Experimental Effects of Cannabis on Pain Sensitivity and Memory: A Scoping Projective Study

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Apart from the growing body of clinical studies, a history of anecdotal evidence support the use of cannabis for pain relief and memory enhancement across the world, But the drug has been found to also significantly impair memory and other cognitive functions. Based on this, the study experimentally investigated whether cannabis can reduce pain sensitivity, its impact on memory and to determine its sex-dependent effects. The study was carried out at the University of XXX, XXXXXXX. A total of twelve (12) Albino rats were investigated in a pretest, post-test design. The experimental material/instruments include plant materials, novel object recognition test and hot plate apparatus. Using IBM SPSS Statistics and Microsoft Excel, descriptive statistics, one-way within subjects repeated measures ANOVA, and paired sample t-test were employed. Two hypotheses guided this study; and findings showed that effects of cannabis on pain sensitivity were sex-dependent and exposure to cannabis use demonstrated a higher pain tolerance; while rats exposed to cannabis showed more effect on male memory than on female memory. The study therefore concluded that cannabis extract revealed significant sex-dependent and dose-dependent effect on pain sensitivity and memory which can be replicated in humans. Cannabis and dependency dose and sex memory stimuli and pain sensitivity albino rats projective experiment Introduction Pain is the alarm system that announces something is not right within the internal system. Pain can occur as a result of sickness or environmental accidents, which usually prompts people to seek for assistance medically or professionally. Seeing that the cause of pain is multifaceted, and some not properly understood, it happens to be a quite irritating to tackle. Organisms are naturally inclined to move away from pain and move towards pleasure, making pain one of the most researched topic in contemporary times in the behavioural sciences (Garagnani et al., 2025 ; Krypotos et al., 2024 ; Sullivana et al., 2025 ; Teichmüller et al., 2024 ). In modern literature, pain sensitivity is often used interchangeably for pain threshold, which according to Torres ( 2017 ) is the least intensity that an individual subjectively starts to sense a stimulus (internal or external) as painful - a varying phenomenon. For instance, pain sensitivity for temperatures may vary based on age factor, and individuals tend to adjust or tolerate frequent exposure to painful experiences, thereby leading to lower pain sensitivity. Till date, medications do not exist to exempt one from some types of extreme pain, and even when some pain reliefs’ medications are administered, they do come with consequential side effects. Hence, the expedition for a more refined pain alleviators will continue for a long time. In view of this, there is urgent need for reviewing the evidence so as to keep health practitioners with up-to-date knowledge. Cannabis has been adopted in the treatment of diverse pain-related conditions, ranging from mild discomforts to the excruciating pains of childbirth. For others cannabis is tantamount to opium aiding in retentive memory; they believe that the effect of cannabis helps them to be more creative, recall things faster and better and gives them a clear perspective on issues. As a generic term, cannabis is adopted implying psychoactive preparations of Cannabis sativa and indica. The usage of cannabis in treating pain, memory and other conditions can be traced back to ancient Chinese texts, dating to 2900 B.C. The three (3) main types of cannabis are sativa, indica and hybrid. Sativas are known for their “head high,” an invigorating, energizing effect that can help reduce anxiety or stress and increase creativity. Secondly, Indicas are connected to complete body effects, including deep relaxation and insomnia reduction. Thirdly, hybrids are designed to combine Indica and Sativa chemistry into various products that give customers more, better options. Although cannabis has been used in medical procedures for centuries, the scientific rationale for its efficacy is not vivid. Although, as summarized by WHO ( 1997 ), cannabis influences cognitive and affective domains as well as learning processes. A report recently released by the National Academies of Sciences (2017), indicate that there is moderate evidence of cannabis use impairing intellectual functioning. Furthermore, cognitive and intelligence deficits have been largely studied among people who regularly use cannabis (Schoeler & Bhattacharyya, 2013 ; Scott et al., 2018 ). Cannabis has also been known to affect the working memory (i.e., a type short-term memory) that typically allow people to store and play around with information for a limited period sufficient to execute any task or properly solve a problem ( Schoeler & Bhattacharyya, 2013 ). For the theoretical perspective of this study, Atkinson-Shiffrin 3-stage model of memory and gate control theory was adopted. The 3-stage model has to do with distinguishing between sensory, short-term, and long-term memories, in which receiving and processing information is paramount. This is followed by storage of the encoded information, and recall or retrieval (Atkinson & Shiffrin, 1968 ). Most of the memory tests that have been employed when investigating the acute effects of cannabis assessed the declarative (explicit) memory system (that is, conscious recall of events/facts), while working memory entails temporary storage of episodic data. At any point in time, issues can erupt, resulting to forgetfulness or amnesia. On the other hand, Gate Control theory stated that pain stimulation is conveyed by tiny fibres – called T-cells that enter the dorsal horn of the spinal cord; and then to the brain, impacting on smaller fibres that transports the pain stimulation (Melzack & Wall, 1965 ). The major thrust of this theory is that pain signal transmission can be influenced by cognitive and emotional processes. Without doubt, cannabis have been empirically used by virtually everyone from all works of life such as policemen, students, young people, clinical patients, public servants etc. resulting to harmful use of drugs, illicit drug use, and have been implicated in coping, treatment and managing stressful and challenging times (Abikoye & Awopetu, 2017 ; Effiong et al., 2017 ; Iloma et al., 2020 ; Iloma et al., 2017 ; lmbur et al., 2021 ; Kgatitswe & Amone-P’Olak, 2017 ; Okechukwu et al., 2022 ; Osuafor et al., 2017 ). A study by Abuhasira et al. ( 2018 ) in which data collected from 2,700 patients found positive results among a slightly younger crowd in their condition after six months of using the drug. In another study, a recent comprehensive review of current data on the health effects of cannabis and cannabinoids, the National Academies of Sciences (2017) determined that adult patients with chronic pain who were treated with cannabis/cannabinoids were more likely to experience a clinically noteworthy reduction in pain symptoms. Another study by Hammell et al. ( 2016 ) noted a significant drop in inflammation and signs of pain, without additional side effects in which they projected that people using CBD oil for arthritis may find relief from their pain. Reiman et al. ( 2017 ) found that 97% of participants reported that they were able to decrease their use of opioids when also using marijuana. Abelev et al. ( 2022 ) indicated more than half of participants experiencing at least one adverse event during the observation period and patients’ reported pain scores were significantly reduced across the cohort. As stated by Baratta et al. ( 2022 ), “Cannabis is a panacea, means that in many countries it is currently possible to use medical cannabis even though the scientific data do not entirely support the signs of efficacy” (p. 13). Schoeler et al. ( 2015 ) while reviewing 88 studies and investigating 7697 healthy and 3261 psychotic individuals, found that cannabis use was significantly linked with impaired global and prospective memory, higher depression, verbal immediate and delayed recall as well as visual recognition in healthy individuals. Schoeler and Bhattacharyya ( 2013 ) found a pattern of interacting factors impacting on the relationship between cannabis use and memory function. Pantoja-Ruiza et al. ( 2022 ) carried out a review and found weak evidence for neuropathic, rheumatic pain, and headache. Gruber et al. ( 2014 ) after administering patients taking marijuana observed that their brains had more activity in the prefrontal cortex, the area associated with cognition, decision-making and executive function. In a clinical trial by McGuire et al. ( 2018 ), they found from the 88 respondents enrolled that people who received CBD reported greater alleviation of symptoms than those who only stuck to their normal medications. The same researchers using a different sample later found that daily marijuana users had the highest risk of developing the condition. Researchers such as Mouro et al. ( 2018 ) found that continued use of either cannabis or cannabis-based drugs impairs memory among adult mice. Despite substantial evidence of the use of cannabis for pain and enhance memory, the literature reports inconsistent findings regarding the longer-term impacts of using cannabis to treat pain and improve memory particularly in Nigeria. Hence, based on empirical evidence on the negative effects of cannabis it is imperative to look further into its contrary effects on learning, recollection and recognition; hence, the present study sought to elucidate the association between cannabis use and pain by examining its effects on albino rats and examining gender differences. In view of the foregoing the study outlines some hypotheses: cannabis will have a significant effect on pain sensitivity and cannabis will have more effect on male’s memory than in females. Method Design and setting A pre-test and post-test design was adapted to establish and compare responses before administration and after administration; while the study was carried out in the Animal House Unit Laboratory Faculty of Pharmacy, Department of Pharmacy and Toxicology at the University of XXX in line with the Basel Declarations of 2010. Experimental animals: A total 12 male and female albino Wistar rats of weight 100 gm were purchased from certified animal vendors and was used for this study. They were maintained in the Animal House Unit of the Department of Pharmacy and Toxicology, University of XXX, XXXXXXX, at a temperature of 30 ± 2°C and 12 h light/dark cycles with free access to food and water. Animals were divided into 3 groups of 4 rats for both pain and memory. Experimental material/instruments Plant materials: Cannabis Indica was purchased from certified vendors with the approval of the office of the National Drug Law Enforcement Agency (NDLEA), XXX, XXXX-XXXX State Command with reference number: UU/FSS/D/30/VOL.I and homogenized using the manual blender. 100gm of the blended leaves was weighed and soaked in 2.5 liter of ethanol and allowed for 96 hours, after which it was filtered and dried for evaporation of ethanol using a student water bath at 46°C for 72hrs. The filtrate was stored in clean glass beaker and refrigerated. The extract was brought out of the refrigerator 2 hours to oral administration. The low dose was taken as 0.5 mg/100 g body weight and high dose HD as 0.8 mg/100 g body weight (Obembe et al., 2015). See appendix for pictures of equipment used. Novel object recognition test: The test relies on as few as three sessions: one habituation session, one training session, and one test session. Training simply involves visual exploration of two identical objects, while the test session involves replacing one of the previously explored objects with a novel object. Because rodents have an innate preference for novelty, a rodent that remembers the familiar object will spend more time exploring the novel object (Ennaceur, 2010). The experimental apparatus used for the object recognition task was an open-field box (in inches, 12 wide, 16 long, 15 deep × 15 high) transparent plastic container. Habituation: Each rat was removed from its home cage and placed in the middle of the open, empty arena and allowed free exploration of the arena for 5 minutes. Apparatus was thoroughly cleaned between rats using ethanol. See appendix for pictures of equipment used. Training : Twenty four hours after habituation, animals were placed back into the arena with two identical objects 4-5inches besides each other in the arena. Free exploration of 10mins was allowed for each animal. Any animal that did not reach a total exploration of 20 seconds per objects was given additional 5 minutes. At the end of the trial, rats were removed and place in the holding cage. The apparatus and objects were cleaned between rats with ethanol. See appendix for pictures of equipment used. Testing: Cannabis sativa was administered to low dose and high dose group, control group was given water. One object used during training (i.e., the familiar object) and one novel object was placed 4-5 inches besides each other and rats were given 10 minutes for exploration. More so, rats were tested twice; for short term memory, 3-5 hours following training and for long term memory 18-21 hours following training. Hot plate test: Thomas scientific hot plate (author regulated) was used for this test. The heated surface of a hot plate was maintained at 55.0 ± 0.5°C. Each albino rat was gently placed on the plate and the time required for the mouse for paw-licking or jumping was taken as the response (Wolff & MacDonald 1994). A 2000ml beaker was placed around the animal to prevent it from moving from the platform and to avoid tissue damage the cutoff time or latency response in the control was taken as 15 seconds. The test was performed before administration to establish baseline responses and was repeated post administration at 15, 30, 60, 90, 120minute interval. See appendix for pictures of equipment used. Administration procedure Hot plate test : This stage shows the doses were administered during the testing of cannabis on pain sensitivity. The dose responses of cannabis were compared to aspirin (an already established pain reliever) to use as a base measurement in observing the effectiveness of cannabis. This was after pre-administration test. Doses were also weight-dependent. Novel object recognition test : This stage indicates the doses administered during the testing of cannabis on memory. The control group was given nothing so the data responses collected from the experimental groups (low & high dose cannabis) can be compared. This serves the purpose of understanding the significant difference between all groups. Doses were calculated and administered using the rat’s weight and the mg/ml. Ethical approval: The authors hereby declare that “Principles of Laboratory animal care” (NIH publication No. 85-23, revised 1985) were followed. All experiments was examined and approved by the Ethics Committee of the University of Uyo, Akwa Ibom state. In addition, towards the end of the study, as professionally required, sodium pentobarbital was administered via intraperitoneal injection, as the euthanasia agent due to its tolerance level of carbon dioxide exposure. Statistical analyses: Descriptive statistic such as mean ± standard error mean (SEM) and standard deviation (SD) were used to present the data and calculate for continuous variables, while frequency as a proportion of the group was calculated for categorical variables. Further, paired sample t-test and one way within subject repeated measure ANOVA was used for hypothesis testing. Lastly, all differences were considered significant at p <0.05 level of significance. Results Data presentation Table 1: Descriptive statistics showing the frequencies, means, standard deviation and standard error means of rats used as subjects in the experiment across the groups. Variables M (Seconds) SD SEM Pretest Male 5.33 .02 .02 Female 6.33 .68 .48 Posttest after cannabis administration Male 15 Min 5.91 .59 .42 Fem 15 Min 10.53 1.33 .94 Male 30 Min 8.67 1.56 1.10 Fem 30 Min 11.21 1.23 .87 Male 60 Min 8.00 .52 .37 Fem 60 Min 13.05 1.29 .92 Male 90 Min 9.71 3.25 2.30 Fem 90 Min 11.13 1.24 .88 Male 120 Min 8.22 1.25 .89 Fem 120 Min 9.94 3.10 2.20 Total 108.03 16.06 11.39 Note: M = Mean; SD = Standard Deviation; SEM = Standard Error Mean; Table 1shows the descriptive statistics for the twelve (12) levels of tests based on the groups (pretest and post-test). The post-test categorized into five (5): 15, 30, 60, 90, and 120 minutes respectively. The results showed little movement within the test scores, the fourth test scoring higher than the first 3, reducing a bit on the fifth test and then the numbers picking up again on the sixth test etc. Table 2: Summary of one-way within subjects Repeated Measures ANOVA showing the effect of cannabis on pain sensitivity among rats. WSE Type III SOS Df MS F Mauchly’s W P SA 63.59 5 12.72 5.01 <0.05 G-G 63.59 2.29 27.76 5.01 <0.05 H-F 63.59 5.01 12.72 5.01 0.05 SA 38.10 15 2.54 G-G 38.10 6.87 5.54 .000 Linear 31.34 1 31.34 9.34 0.55 Quadratic 32.14 1 32.14 13.40 .035 Cubic .05 1 .05 .05 .832 WL - 3 272.26 .045 Note: WSE = Within Subjects Effect ; SOS = Sum Of Squares; df = Degree of Freedom; MS = Mean Square; SA = Sphericity Assumed; G-G = Greenhouse-Geisser; H-F = Huynh-Feldt; LB = Lower Bound; WL = Wilks’ lambda; SE = Standard Error. From the one-way within subjects repeated ANOVA result in Table 2, rats being exposed to cannabis demonstrated higher pain tolerance as can be seen from the Mauchly's Test (Greenhouse-Geisser and Huynh-Feldt corrections) and the pairwise comparisons. The mean difference further confirms this statistical assumption as rats given the placebo (pretest) reported a mean score in pain sensitivity of 5.83 and SD of 0.70. The Wilks’ lambda shows the results of the regression modeling which is significant. Post 15 minutes of administering cannabis the following was observed, (Mean = 8.22; SD = 2.80); for post 30 minutes, (Mean = 9.94; SD = 1.86); post 60 minutes, (Mean = 10.52; SD = 3.02); post 90 minutes, (Mean = 10.42; SD = 2.17); and post 120 minutes, (Mean = 9.08; SD = 2.17). The polynomial contrasts gives us an idea whether the dependent variable (pain sensitivity) data looks like a linear line, quadratic or cubic shape. From the results above, the data was more quadratic in shape than linear, (p = .055 vs p = .035). Mauchly's Test tests the null hypothesis that the error covariance of the orthonormalized transformed dependent variable is proportional to an identity matrix. In this case, it was done by consulting the Epsilon titles (Greenhouse-Geisser and Huynh-Feldt corrections). In the example of this study, the assumption of sphericity has not been met because the Mauchly's Test is significant. This means that the F-values of our repeated measures ANOVA are likely to be too large. This was automatically corrected by decreasing the degrees of freedom used by SPSS. Hence, Table 2 shows that the Greenhouse-Geisser correction has decreased the degrees of freedom from 5 to 2.29 in the first instance. Further, the pairwise comparison revealed that the point of significance within the six (6) levels examined (pretest/baseline, post 15 minutes, post 30 minutes, post 60 minutes, post 90 minutes, and post 120 minutes). The points of significance were between pretest and post 30 minutes post administration of cannabis (SE = 0.65, P<0.05); between pretest and post 60 minutes post administration of cannabis (SE = 1.31, P<0.05); and between 15 minutes post cannabis administration and post 60 minutes post administration of cannabis (SE = 0.13, p <0.05). In summary, six repeated tests were administered to the rats. The repeated measures ANOVA show that achieved scores (in time) on pain sensitivity are significantly different. A pairwise comparison identifies these differences as test 1 (pretest), 2 (15 minutes post-test), test 3 (30 minutes post-test) and test 4 (60 minutes post-test) being significantly different from each other. Thus, the first hypothesis which states that cannabis will have a significant effect on pain sensitivity was sustained. Table 3: Summary of dependent samples t-test showing the paired difference of male and female rats that were given cannabis with respect to their effect on memory. Conditions Criterion Mean SD Correlation Sig. PM T P Male MY 101.38 40.92 0.760 <0.05 23.75 4.31 <0.05 Female MY 77.63 35.59 Note: PM = Paired Mean; SD = Standard Deviation; MY = Memory. Table 3 shows the statistics of male rats and female rats that were given cannabis. Dependent t-test results show that on the average, throughout the experiment, male rats given cannabis showed higher levels of memory (recognition) Mean = 101.38 seconds than female rats Mean = 77.63 seconds. However, the matched t-test shows a t-value of t = 4.31 with 46 degrees of freedom. The dependent t-test is highly significant with ( p <0.05). A matched t-test correlation found a high positive correlation that is significant with r = 0.760, p <0.05. It can therefore be assumed that pairing of data had a strong impact on the power of t-test. Summarily, the dependent samples t-test showed an average reduction in recognition (memory recall) by 23.75 seconds in the sample of 16 rats. From the results above the second hypothesis which states that cannabis will have more effect on males memory than in females was confirmed; with a 95% confidence that the observed reduction in memory can also be found in the general population of rats; with a 5% error rate that the difference in mean scores will be between 12.36 to 35.14. Discussion The study explored experimental effect of cannabis on pain sensitivity and memory using 12 albino rats. The first hypothesis which stated that there will be a significant effect of cannabis administration on pain sensitivity was accepted. It was found that cannabis significantly reduced pain sensitivity across all experimental levels. This is consistent with the findings of Abuhasira et al. (2018) who found that cannabis improved chronic pain in slightly younger participants. The findings was also in-line with the study of Abelev et al. (2022) who observed that more than half of participants experienced at least one adverse events during the observation period. The finding of the study also supported the study of the American Associates and Bengurion University of the Neger (2018) whose findings revealed that cannabis use might be a positive alternative for older folks looking for relief. Furthermore, the findings of the study was also in-line with the study of Haroutounian et al. (2016) whose findings showed that cannabis inhalation influences subjects’ sensitivity to pain. The second hypothesis which stated that Cannabis will have more effect on male memory than females was accepted as male rats given cannabis showed a decrease in recognition memory task. In supporting evidence, Cutler et al. (2021) revealed a number of sex differences in the acute effects of cannabis intoxication as men were more likely than women to report memory improvement when intoxicated. This was inconsistent with findings from Tseng and Craft (2004) and Blaes et al. (2019) who found that exposure to cannabis smoke had no effect on male rats' performance, but surprisingly, enhanced working memory accuracy in females. Based on observations and findings of this study, the risk of cannabis use on memory outweighs the benefit as cannabis may not necessarily relieve pain or have an analgesic effect but may distract you enough, thereby increasing pain tolerance. Conclusively, this study investigated the effect of cannabis extract on pain sensitivity and memory using Albino rats. A total of 12 male and female albino Wistar rats of weight 100 gm were used for this study. They were maintained at a temperature of 30 ± 2°C and 12 h light/dark cycles with free access to food and water. Cannabis sativa was purchased with the approval of the office of the National Drug Law Enforcement Agency (NDLEA), XXX, XXXX-XXXX State and homogenized using the manual blender. 100g of the blended leaves was weighed and soaked in 2.5 liter of ethanol and allowed for 96 hours, after which it was filtered and dried for evaporation of ethanol using a student water bath at 46°C for 72hrs. The filtrate was stored in clean glass beaker and refrigerated. The extract was brought out of the refrigerator 2 hours to oral administration. The low dose was taken as 0.5 ± 0.1 mg/100 g body weight and high dose HD as 0.8 mg/100 g body weight. Thomas scientific hot plate (author regulated) was used for this test was used to test pain sensitivity. Conclusion, recommendations and study limitations The analysis concluded that cannabis extract have significant effect on pain sensitivity and memory. This result sheds light into the effects of cannabis strain on individual working memory as indica is high in CBD. Since results revealed that cannabis significantly improved memory function in long term memory task than in short term memory task, it is safe to say that cannabis has a temporary effect on cognitive function. Based on findings of this study, Cannabis indica is clearly of therapeutical benefit to not just animals but could be projected to humans. In view of this,the findings of this study had very crucial to Ministry of health, clinical psychologist, pharmacist, drug user, researchers and the general public. Thus, the following recommendations are made based on the findings of the study. Medical doctors, pharmacists, psychologist and other health practitioners can recommend a greater dose of cannabis if high in CBD but a lesser dose with THC for people suffering from pain. Cannabis administration also exhibits sex-dependent effects and improves pain threshold in females than in males which makes it a supplementary treatment for pain in females than males. Furthermore, it is also implicated that continuous and higher use of cannabis have negative effect on memory, especially in adolescents and it is also dependent on the cannabis strain (sativa or indica). Hence, it is recommended that government and health organizations set platforms where enlightenment programs about the continuous use of cannabis will be made possible. Nevertheless, some limitations were observed in the course of this study. First, the study failed to differentiate between the types of memory (i.e., implicit, explicit, spatial etc.); hence future studies should attempt to correct this. Other issues were irregular light and sound conditions during the experiment; experimental error in handling, inadequate measuring devices/analysis. A major problem is that overtime the rats may show the necessary response behaviour such as hind paw licking or mouthing and jumping a few seconds after being carried to the hotplate as this ascertains their removal from it. There was a disadvantage of memory test. Also, exploration levels may vary from low to being inconsistent. Hence, exploratory activity can increase via elevated open-space platform or through deprivations (such as food or rewards). More so, differences in observations could be difficult to observe in a typical experimental manipulation; therefore, the necessity to crosscheck every observation and recording of activity during experiments, analysis and interpretation of results from the procedure. Mainly, some suggestions for future research were stated: There are different tests to measure different kinds of pain. It is important to specify the kind of pain to measure and focus the research on drug of choice's ability to eliminate or moderately reduce sensitivity to that particular pain. In which case, using variety of pain measurement options so as to properly evaluate anti-nociceptive effect of drug in all verification is utmost. As there is different rats’ strain, to truly say that cannabis has a significant effect on memory, researches should be done on the different strains and sex, as well as MRI scans to validate results. Declarations Acknowledgements : Special thanks to members and staff of Animal House Unit Laboratory, Department of Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom state for providing the researchers with the needed environment and some apparatus to conveniently conduct this experimental study. Declaration: The authors declare that there is no conflict of interest. Funding The authors received no financial support for the research from any institution or individual. Animal ethics and guidelines Principles of Laboratory animal care” (NIH publication No. 85-23, revised 1985) were followed. All experiments was examined and approved by the Ethics Committee, Department of Psychology, University of Uyo, Akwa Ibom state after proper scrutiny; whereasthe National Drug Law Enforcement Agency (NDLEA), Uyo, Akwa-Ibom State Command with ref no. UU/FSS/D/30/VOL.I (2021) approved the experimental use of cannabis by researchers solely for this study. Ethics approval and consent to participate The present experimental study on albino wistar rats (vertebrates) complied with the Basel Declarations of 2010 which amongst other things includes greater transparency, trust and communication in the use of animals in experimental studies in addition to the 3Rs (i.e., Reduction, Refinement, and Replacement) in animal research. 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Pain mechanisms: A new theory. Science. 1965;150:971–9. Mouro FM, Ribeiro JA, Sebastião AM, Dawson N. Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity. J Neurochem. 2018 https://doi:10.1111/jnc. 14549 . National Academies of Sciences, Engineering, and Medicine. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: National Academies; 2017. https://doi:10.17226/24625 . Obembe AO, Ominini GC, Okon UA, Okpo-ene AI, Ikpi DE. Hematological and immunological effects of cannabis sativa on Albino Wistar Rats. Br J Med Med Res. 2015;7(1):52–60. https://doi:10.9734/BJMMR/2015/15201 . Okechukwu G–P, Nnam MU, Obadimu CO, Iloma DO, Offu P, Okpata F, Nwakanma EU. COVID-19 lockdown related stress among young adults: The role of drug use disorder, neurotic health symptoms, and pathological smartphone use. J Forensic Psychol Res Pract. 2022;1–13. https://doi:10.1080/24732850.2022.2102956 . Osuafor GN, Maputle SM, Netshikweta L. Religiosity as a protective factor against alcohol and substance use among first-year students in a South African University. Afr J Drug Alcohol Stud. 2017;16(2):69–81. https://www.ajol.info/index.php/ajdas/issue/view/19729 . Pantoja-Ruiza C, Restrepo-Jimeneza P, Casta˜neda-Cardonab C, Ferreirósc A, Rosselli D. Cannabis and pain: A scoping review. Brazilian J Anesthesiology. 2022;72(1):142–51. https://doi.org/10.1016/j.bjane . Reiman A, Welty M, Solomon P. Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report. Cannabis Cannabinoid Res. 2017;2(1):160–6. https://doi.org/10.1089/can.2017.0012 . Schoeler T, Bhattacharyya S. The effect of cannabis use on memory function: An update. Subst Abuse Rehabilitation. 2013;4:11–27. http://dx.doi.org/10.2147/SAR.S25869 . Schoeler T, Kambeitz J, Behlke I, Murray R, Bhattacharyya S. The effects of cannabis on memory function in users with and without a psychotic disorder: Findings from a combined meta-analysis. Psychol Med. 2015;1–12. https://doi:10.1017/S0033291715001646 . Scott JC, Slomiak ST, Jones JD, Rosen A, Moore TM, Gur RC. Association of cannabis with cognitive functioning in adolescents and young adults: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2018;75(6):585–95. https://doi.org/10.1001/jamapsychiatry.2018.0335 . Sullivana MD, Amanda C, de Williams C. The social nature of human pain. Pain. 2025;166:20–3. http://dx.doi.org/10.1097/j.pain.0000000000003250 . Teichmüller K, Kübler A, Rittner HL, Kindl G-K. Avoidance and endurance responses to pain before and with advanced chronification: preliminary results from a questionnaire survey in adult patients with non-cancer pain conditions. J Pain Res. 2024;17:2473–81. https://doi:10.2147/JPR.S464509 . Torres B. (2017). Pain Tolerance and Pain Threshold. Novus Pain Centre Retrieved from https://novusspinecenter.com/blog/pain/pain-tolerance-pain-threshold# Tseng AH, Craft RM. CB(1) receptor mediation of cannabinoid behavioral effects in male and female rats. Psychopharmacology. 2004;172:25–30. WHO. Cannabis: A health perspective and research agenda. Geneva: World Health Organization; 1997. p. 46. Additional Declarations No competing interests reported. Supplementary Files CANNABISApparatusMain.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6512894","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471916153,"identity":"7003494b-8422-4510-81af-756500b78cc5","order_by":0,"name":"Melissa Ernest Micheal","email":"","orcid":"","institution":"University of Uyo","correspondingAuthor":false,"prefix":"","firstName":"Melissa","middleName":"Ernest","lastName":"Micheal","suffix":""},{"id":471916154,"identity":"2dbd322e-87ee-417d-a27e-698ec4b8a42d","order_by":1,"name":"David Okanandu Iloma","email":"data:image/png;base64,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","orcid":"","institution":"Topfaith University Mkpatak","correspondingAuthor":true,"prefix":"","firstName":"David","middleName":"Okanandu","lastName":"Iloma","suffix":""},{"id":471916155,"identity":"9912e8d6-bca5-4211-a381-e05657dcc424","order_by":2,"name":"Clement Olusegun Obadimu","email":"","orcid":"","institution":"University of Uyo","correspondingAuthor":false,"prefix":"","firstName":"Clement","middleName":"Olusegun","lastName":"Obadimu","suffix":""}],"badges":[],"createdAt":"2025-04-23 13:08:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6512894/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6512894/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95801139,"identity":"9853e58b-bc53-4f23-9b86-d509d41a0620","added_by":"auto","created_at":"2025-11-13 08:24:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":906084,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6512894/v1/9ce21fce-c403-4c96-9ebc-4c1a21ee9e0e.pdf"},{"id":84867466,"identity":"bf4f17d5-4e82-4ca2-9272-6bab54ef42c4","added_by":"auto","created_at":"2025-06-18 08:31:03","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":331434,"visible":true,"origin":"","legend":"","description":"","filename":"CANNABISApparatusMain.docx","url":"https://assets-eu.researchsquare.com/files/rs-6512894/v1/c295bef97965e6c5bd16bd5f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eExperimental Effects of Cannabis on Pain Sensitivity and Memory: A Scoping Projective Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePain is the alarm system that announces something is not right within the internal system. Pain can occur as a result of sickness or environmental accidents, which usually prompts people to seek for assistance medically or professionally. Seeing that the cause of pain is multifaceted, and some not properly understood, it happens to be a quite irritating to tackle. Organisms are naturally inclined to move away from pain and move towards pleasure, making pain one of the most researched topic in contemporary times in the behavioural sciences (Garagnani et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Krypotos et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Sullivana et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Teichm\u0026uuml;ller et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). In modern literature, pain sensitivity is often used interchangeably for pain threshold, which according to Torres (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) is the least intensity that an individual subjectively starts to sense a stimulus (internal or external) as painful - a varying phenomenon. For instance, pain sensitivity for temperatures may vary based on age factor, and individuals tend to adjust or tolerate frequent exposure to painful experiences, thereby leading to lower pain sensitivity. Till date, medications do not exist to exempt one from some types of extreme pain, and even when some pain reliefs\u0026rsquo; medications are administered, they do come with consequential side effects. Hence, the expedition for a more refined pain alleviators will continue for a long time.\u003c/p\u003e \u003cp\u003eIn view of this, there is urgent need for reviewing the evidence so as to keep health practitioners with up-to-date knowledge. Cannabis has been adopted in the treatment of diverse pain-related conditions, ranging from mild discomforts to the excruciating pains of childbirth. For others cannabis is tantamount to opium aiding in retentive memory; they believe that the effect of cannabis helps them to be more creative, recall things faster and better and gives them a clear perspective on issues. As a generic term, cannabis is adopted implying psychoactive preparations of Cannabis sativa and indica. The usage of cannabis in treating pain, memory and other conditions can be traced back to ancient Chinese texts, dating to 2900 B.C. The three (3) main types of cannabis are sativa, indica and hybrid. Sativas are known for their \u0026ldquo;head high,\u0026rdquo; an invigorating, energizing effect that can help reduce anxiety or stress and increase creativity. Secondly, Indicas are connected to complete body effects, including deep relaxation and insomnia reduction. Thirdly, hybrids are designed to combine Indica and Sativa chemistry into various products that give customers more, better options. Although cannabis has been used in medical procedures for centuries, the scientific rationale for its efficacy is not vivid. Although, as summarized by WHO (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e1997\u003c/span\u003e), cannabis influences cognitive and affective domains as well as learning processes. A report recently released by the National Academies of Sciences (2017), indicate that there is moderate evidence of cannabis use impairing intellectual functioning. Furthermore, cognitive and intelligence deficits have been largely studied among people who regularly use cannabis (Schoeler \u0026amp; Bhattacharyya, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Scott et al., \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Cannabis has also been known to affect the working memory (i.e., a type short-term memory) that typically allow people to store and play around with information for a limited period sufficient to execute any task or properly solve a problem \u003cb\u003e(\u003c/b\u003eSchoeler \u0026amp; Bhattacharyya, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2013\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFor the theoretical perspective of this study, Atkinson-Shiffrin 3-stage model of memory and gate control theory was adopted. The 3-stage model has to do with distinguishing between sensory, short-term, and long-term memories, in which receiving and processing information is paramount. This is followed by storage of the encoded information, and recall or retrieval (Atkinson \u0026amp; Shiffrin, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e1968\u003c/span\u003e). Most of the memory tests that have been employed when investigating the acute effects of cannabis assessed the declarative (explicit) memory system (that is, conscious recall of events/facts), while working memory entails temporary storage of episodic data. At any point in time, issues can erupt, resulting to forgetfulness or amnesia. On the other hand, Gate Control theory stated that pain stimulation is conveyed by tiny fibres \u0026ndash; called T-cells that enter the dorsal horn of the spinal cord; and then to the brain, impacting on smaller fibres that transports the pain stimulation (Melzack \u0026amp; Wall, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e1965\u003c/span\u003e). The major thrust of this theory is that pain signal transmission can be influenced by cognitive and emotional processes.\u003c/p\u003e \u003cp\u003eWithout doubt, cannabis have been empirically used by virtually everyone from all works of life such as policemen, students, young people, clinical patients, public servants etc. resulting to harmful use of drugs, illicit drug use, and have been implicated in coping, treatment and managing stressful and challenging times (Abikoye \u0026amp; Awopetu, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Effiong et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Iloma et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Iloma et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; lmbur et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Kgatitswe \u0026amp; Amone-P\u0026rsquo;Olak, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Okechukwu et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Osuafor et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). A study by Abuhasira et al. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) in which data collected from 2,700 patients found positive results among a slightly younger crowd in their condition after six months of using the drug. In another study, a recent comprehensive review of current data on the health effects of cannabis and cannabinoids, the National Academies of Sciences (2017) determined that adult patients with chronic pain who were treated with cannabis/cannabinoids were more likely to experience a clinically noteworthy reduction in pain symptoms. Another study by Hammell et al. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) noted a significant drop in inflammation and signs of pain, without additional side effects in which they projected that people using CBD oil for arthritis may find relief from their pain. Reiman et al. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) found that 97% of participants reported that they were able to decrease their use of opioids when also using marijuana. Abelev et al. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) indicated more than half of participants experiencing at least one adverse event during the observation period and patients\u0026rsquo; reported pain scores were significantly reduced across the cohort. As stated by Baratta et al. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), \u0026ldquo;Cannabis is a panacea, means that in many countries it is currently possible to use medical cannabis even though the scientific data do not entirely support the signs of efficacy\u0026rdquo; (p. 13). Schoeler et al. (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) while reviewing 88 studies and investigating 7697 healthy and 3261 psychotic individuals, found that cannabis use was significantly linked with impaired global and prospective memory, higher depression, verbal immediate and delayed recall as well as visual recognition in healthy individuals. Schoeler and Bhattacharyya (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2013\u003c/span\u003e) found a pattern of interacting factors impacting on the relationship between cannabis use and memory function. Pantoja-Ruiza et al. (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) carried out a review and found weak evidence for neuropathic, rheumatic pain, and headache. Gruber et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2014\u003c/span\u003e) after administering patients taking marijuana observed that their brains had more activity in the prefrontal cortex, the area associated with cognition, decision-making and executive function. In a clinical trial by McGuire et al. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2018\u003c/span\u003e), they found from the 88 respondents enrolled that people who received CBD reported greater alleviation of symptoms than those who only stuck to their normal medications. The same researchers using a different sample later found that daily marijuana users had the highest risk of developing the condition. Researchers such as Mouro et al. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) found that continued use of either cannabis or cannabis-based drugs impairs memory among adult mice. Despite substantial evidence of the use of cannabis for pain and enhance memory, the literature reports inconsistent findings regarding the longer-term impacts of using cannabis to treat pain and improve memory particularly in Nigeria. Hence, based on empirical evidence on the negative effects of cannabis it is imperative to look further into its contrary effects on learning, recollection and recognition; hence, the present study sought to elucidate the association between cannabis use and pain by examining its effects on albino rats and examining gender differences. In view of the foregoing the study outlines some hypotheses: cannabis will have a significant effect on pain sensitivity and cannabis will have more effect on male\u0026rsquo;s memory than in females.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003e\u003cstrong\u003eDesign and setting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA pre-test and post-test design was adapted to establish and compare responses before administration and after administration; while the study was carried out in the Animal House Unit Laboratory Faculty of Pharmacy, Department of Pharmacy and Toxicology at the University of XXX in line with the Basel Declarations of 2010.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExperimental animals:\u0026nbsp;\u003c/strong\u003eA total 12 male and female albino Wistar rats of weight 100 gm were purchased from certified animal vendors and was used for this study. They were maintained in the Animal House Unit of the Department of Pharmacy and Toxicology, University of XXX, XXXXXXX, at a temperature of 30 ± 2°C and 12 h light/dark cycles with free access to food and water. Animals were divided into 3 groups of 4 rats for both pain and memory.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExperimental material/instruments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePlant materials:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eCannabis Indica was purchased from certified vendors with the approval of the office of the National Drug Law Enforcement Agency (NDLEA), XXX, XXXX-XXXX State Command with reference number: UU/FSS/D/30/VOL.I and homogenized using the manual blender. 100gm of the blended leaves was weighed and soaked in 2.5 liter of ethanol and allowed for 96 hours, after which it was filtered and dried for evaporation of ethanol using a student water bath at 46°C for 72hrs. The filtrate was stored in clean glass beaker and refrigerated. The extract was brought out of the refrigerator 2 hours to oral administration. The low dose was taken as 0.5 mg/100 g body weight and high dose HD as 0.8 mg/100 g body weight (Obembe et al., 2015). See appendix for pictures of equipment used.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eNovel object recognition test:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eThe test relies on as few as three sessions: one habituation session, one training session, and one test session. Training simply involves visual exploration of two identical objects, while the test session involves replacing one of the previously explored objects with a novel object. Because rodents have an innate preference for novelty, a rodent that remembers the familiar object will spend more time exploring the novel object\u0026nbsp;(Ennaceur, 2010). The experimental apparatus used for the object recognition task was an open-field box (in inches, 12 wide, 16 long, 15 deep × 15 high) transparent plastic container.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eHabituation:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eEach rat was removed from its home cage and placed in the middle of the open, empty arena and allowed free exploration of the arena for 5 minutes. Apparatus was thoroughly cleaned between rats using ethanol. See appendix for pictures of equipment used.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTraining\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u0026nbsp;\u003c/em\u003eTwenty four hours after habituation, animals were placed back into the arena with two identical objects 4-5inches besides each other in the arena. Free exploration of 10mins was allowed for each animal. Any animal that did not reach a total exploration of 20 seconds per objects was given additional 5 minutes. At the end of the trial, rats were removed and place in the holding cage. The apparatus and objects were cleaned between rats with ethanol. See appendix for pictures of equipment used.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTesting:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eCannabis sativa was administered to low dose and high dose group, control group was given water. One object used during training (i.e., the familiar object) and one novel object was placed 4-5 inches besides each other and rats were given 10 minutes for exploration. More so, rats were tested twice; for short term memory, 3-5 hours following training and for long term memory 18-21 hours following training.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHot plate test:\u0026nbsp;\u003c/strong\u003eThomas scientific hot plate (author regulated) was used for this test. The heated surface of a hot plate was maintained at 55.0 ± 0.5°C. Each albino rat was gently placed on the plate and the time required for the mouse for paw-licking or jumping was taken as the response (Wolff \u0026amp; MacDonald 1994). A 2000ml beaker was placed around the animal to prevent it from moving from the platform and to avoid tissue damage the cutoff time or latency response in the control was taken as 15 seconds. The test was performed before administration to establish baseline responses and was repeated post administration at 15, 30, 60, 90, 120minute interval. See appendix for pictures of equipment used.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdministration procedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eHot plate test\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eThis stage shows the doses were administered during the testing of cannabis on pain sensitivity. The dose responses of cannabis were compared to aspirin (an already established pain reliever) to use as a base measurement in observing the effectiveness of cannabis. This was after pre-administration test. Doses were also weight-dependent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eNovel object recognition test\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eThis stage indicates the doses administered during the testing of cannabis on memory. The control group was given nothing so the data responses collected from the experimental groups (low \u0026amp; high dose cannabis) can be compared. This serves the purpose of understanding the significant difference between all groups. Doses were calculated and administered using the rat’s weight and the mg/ml.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u0026nbsp;\u003c/strong\u003eThe authors hereby declare that “Principles of Laboratory animal care” (NIH publication No. 85-23, revised 1985) were followed. All experiments was examined and approved by the Ethics Committee of the University of Uyo, Akwa Ibom state. In addition, towards the end of the study, as professionally required, sodium pentobarbital was administered via intraperitoneal injection, as the euthanasia agent due to its tolerance level of carbon dioxide exposure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses:\u0026nbsp;\u003c/strong\u003eDescriptive statistic such as mean ± standard error mean (SEM) and standard deviation (SD) were used to present the data and calculate for continuous variables, while frequency as a proportion of the group was calculated for categorical variables. Further, paired sample t-test and one way within subject repeated measure ANOVA was used for hypothesis testing. Lastly, all differences were considered significant at \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05 level of significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eData presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Descriptive statistics showing the frequencies, means, standard deviation and standard error means of rats used as subjects in the experiment across the groups.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"479\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eM (Seconds)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSEM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePretest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePosttest after cannabis administration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale 15 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFem 15 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale 30 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFem 30 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale 60 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFem 60 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale 90 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFem 90 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale 120 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFem 120 Min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e108.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e16.06\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e11.39\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u0026nbsp;\u003c/strong\u003eM = Mean; SD = Standard Deviation; SEM = Standard Error Mean;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 1shows the descriptive statistics for the twelve (12) levels of tests based on the groups (pretest and post-test). The post-test categorized into five (5): 15, 30, 60, 90, and 120 minutes respectively. \u0026nbsp;The results showed little movement within the test scores, the fourth test scoring higher than the first 3, reducing a bit on the fifth test and then the numbers picking up again on the sixth test etc.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Summary of one-way within subjects Repeated Measures ANOVA showing the effect of cannabis on pain sensitivity among rats.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"599\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWSE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType III SOS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDf\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMauchly’s W\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e63.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eG-G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e63.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e27.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eH-F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e63.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e63.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e63.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e38.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eG-G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e38.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLinear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eQuadratic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.035\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCubic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.832\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e272.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.045\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u0026nbsp;\u003c/strong\u003eWSE = Within Subjects Effect ; SOS = Sum Of Squares; df = Degree of Freedom; MS = Mean Square; SA = Sphericity Assumed; G-G = Greenhouse-Geisser; H-F = Huynh-Feldt; LB = Lower Bound; WL = Wilks’ lambda; SE = Standard Error.\u003c/p\u003e\n\u003cp\u003eFrom the one-way within subjects repeated ANOVA result in Table 2, rats being exposed to cannabis demonstrated higher pain tolerance as can be seen from the Mauchly's Test (Greenhouse-Geisser and Huynh-Feldt corrections) and the pairwise comparisons. The mean difference further confirms this statistical assumption as rats given the placebo (pretest) reported a mean score in pain sensitivity of 5.83 and SD of 0.70. The Wilks’ lambda shows the results of the regression modeling which is significant. Post 15 minutes of administering cannabis the following was observed, (Mean = 8.22; SD = 2.80); for post 30 minutes, (Mean = 9.94; SD = 1.86); post 60 minutes, (Mean = 10.52; SD = 3.02); post 90 minutes, (Mean = 10.42; SD = 2.17); and post 120 minutes, (Mean = 9.08; SD = 2.17). The polynomial contrasts gives us an idea whether the dependent variable (pain sensitivity) data looks like a linear line, quadratic or cubic shape. From the results above, the data was more quadratic in shape than linear, (p = .055 vs p = .035). Mauchly's Test tests the null hypothesis that the error covariance of the orthonormalized transformed dependent variable is proportional to an identity matrix. In this case, it was done by consulting the Epsilon titles (Greenhouse-Geisser and Huynh-Feldt corrections). In the example of this study, the assumption of sphericity has not been met because the Mauchly's Test is significant. This means that the F-values of our repeated measures ANOVA are likely to be too large. This was automatically corrected by decreasing the degrees of freedom used by SPSS. Hence, Table 2 shows that the Greenhouse-Geisser correction has decreased the degrees of freedom from 5 to 2.29 in the first instance.\u003c/p\u003e\n\u003cp\u003eFurther, the pairwise comparison revealed that the point of significance within the six (6) levels examined (pretest/baseline, post 15 minutes, post 30 minutes, post 60 minutes, post 90 minutes, and post 120 minutes). The points of significance were between pretest and post 30 minutes post administration of cannabis (SE = 0.65, P\u0026lt;0.05); between pretest and post 60 minutes post administration of cannabis (SE = 1.31, P\u0026lt;0.05); and between 15 minutes post cannabis administration and post 60 minutes post administration of cannabis (SE = 0.13, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05). \u0026nbsp;In summary, six repeated tests were administered to the rats. The repeated measures ANOVA show that achieved scores (in time) on pain sensitivity are significantly different. A pairwise comparison identifies these differences as test 1 (pretest), 2 (15 minutes post-test), test 3 (30 minutes post-test) and test 4 (60 minutes post-test) being significantly different from each other. Thus, the first hypothesis which states that\u0026nbsp;cannabis will have a significant effect on pain sensitivity was sustained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Summary of dependent samples t-test showing the paired difference of male and female rats that were given cannabis with respect to their effect on memory.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"606\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eConditions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCriterion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCorrelation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Sig.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e101.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;0.760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.05\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e23.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e4.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e77.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e35.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u0026nbsp;\u003c/strong\u003ePM = Paired Mean; SD = Standard Deviation; MY = Memory.\u003c/p\u003e\n\u003cp\u003eTable 3 shows the statistics of male rats and female rats that were given cannabis. Dependent t-test results show that on the average, throughout the experiment, male rats given cannabis showed higher levels of memory (recognition) Mean = 101.38 seconds than female rats Mean = 77.63 seconds. However, the matched t-test shows a t-value of t = 4.31 with 46 degrees of freedom. The dependent t-test is highly significant with (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05). A matched t-test correlation found a high positive correlation that is significant with \u003cem\u003er\u003c/em\u003e = 0.760, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05. It can therefore be assumed that pairing of data had a strong impact on the power of t-test. Summarily, the dependent samples t-test showed an average reduction in recognition (memory recall) by 23.75 seconds in the sample of 16 rats. From the results above the second hypothesis which states that cannabis will have more effect on males memory than in females was confirmed; with a 95% confidence that the observed reduction in\u0026nbsp;memory can also be found in the general population of rats; with a 5% error rate that the difference in\u0026nbsp;mean\u0026nbsp;scores will be between\u0026nbsp;12.36 to 35.14.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe study explored experimental effect of cannabis on pain sensitivity and memory using 12 albino rats. The first hypothesis which stated that there will be a\u0026nbsp;significant effect of cannabis administration on pain sensitivity was accepted. It was found that cannabis significantly reduced pain sensitivity across all experimental levels. This is consistent with the findings of Abuhasira et al. (2018) who found that cannabis improved chronic pain in slightly younger participants. The findings was also in-line with the study of Abelev et al. (2022) who observed that more than half of participants experienced at least one adverse events during the observation period. The finding of the study also supported the study of the American Associates and Bengurion University of the Neger (2018) whose findings revealed that cannabis use might be a positive alternative for older folks looking for relief. Furthermore, the findings of the study was also in-line with the study of \u003cstrong\u003eHaroutounian et al. (2016) whose findings showed that\u0026nbsp;\u003c/strong\u003ecannabis inhalation influences subjects’ sensitivity to pain.\u003c/p\u003e\n\u003cp\u003eThe second hypothesis which stated that Cannabis will have more effect on male memory than females was accepted as male rats given cannabis showed a decrease in recognition memory task. In supporting evidence, Cutler et al. (2021) revealed a number of sex differences in the acute effects of cannabis intoxication as men were more likely than women to report memory improvement when intoxicated. \u0026nbsp;This was inconsistent with findings from Tseng and Craft (2004) and Blaes et al. (2019) who found that exposure to cannabis smoke had no effect on male rats' performance, but surprisingly, enhanced working memory accuracy in females. Based on observations and findings of this study, the risk of cannabis use on memory outweighs the benefit as cannabis may not necessarily relieve pain or have an analgesic effect but may distract you enough, thereby increasing pain tolerance. Conclusively, this study investigated the effect of cannabis extract on pain sensitivity and memory using Albino rats. A total of 12 male and female albino Wistar rats of weight 100 gm were used for this study. They were maintained at a temperature of 30 ± 2°C and 12 h light/dark cycles with free access to food and water. Cannabis sativa was purchased with the approval of the office of the National Drug Law Enforcement Agency (NDLEA), XXX, XXXX-XXXX State and homogenized using the manual blender. 100g of the blended leaves was weighed and soaked in 2.5 liter of ethanol and allowed for 96 hours, after which it was filtered and dried for evaporation of ethanol using a student water bath at 46°C for 72hrs. The filtrate was stored in clean glass beaker and refrigerated. The extract was brought out of the refrigerator 2 hours to oral administration. The low dose was taken as 0.5 ± 0.1 mg/100 g body weight and high dose HD as 0.8 mg/100 g body weight. Thomas scientific hot plate (author regulated) was used for this test was used to test pain sensitivity.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion, recommendations and study limitations","content":"\u003cp\u003eThe analysis concluded that cannabis extract have significant effect on pain sensitivity and memory. This result sheds light into the effects of cannabis strain on individual working memory as indica is high in CBD. Since results revealed that cannabis significantly improved memory function in long term memory task than in short term memory task, it is safe to say that cannabis has a temporary effect on cognitive function. Based on findings of this study, Cannabis indica is clearly of therapeutical benefit to not just animals but could be projected to humans.\u0026nbsp;In view of this,the findings of this study had very crucial to Ministry of health, clinical psychologist, pharmacist, drug user, researchers and the general public. Thus, the following recommendations are made based on the findings of the study. Medical doctors, pharmacists, psychologist and other health practitioners can recommend a greater dose of cannabis if high in CBD but a lesser dose with THC for people suffering from pain. Cannabis administration also exhibits sex-dependent effects and improves pain threshold in females than in males which makes it a supplementary treatment for pain in females than males. Furthermore, it is also implicated that continuous and higher use of cannabis have negative effect on memory, especially in adolescents and it is also dependent on the cannabis strain (sativa or indica). Hence, it is recommended that government and health organizations set platforms where enlightenment programs about the continuous use of cannabis will be made possible.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNevertheless, some limitations were observed in the course of this study. First, the\u0026nbsp;study failed to differentiate between the types of memory (i.e., implicit, explicit, spatial etc.); hence future studies should attempt to correct this.\u0026nbsp;Other issues were irregular light and sound conditions during the experiment; experimental error in handling, inadequate measuring devices/analysis. A major problem is that overtime the rats may show the necessary response behaviour such as hind paw licking or mouthing and jumping a few seconds after being carried to the hotplate as this ascertains their removal from it. There was a disadvantage of memory test. Also, exploration levels may vary from low to being inconsistent. Hence, exploratory activity can increase via elevated open-space platform or through deprivations (such as food or rewards).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMore so, differences in observations could be difficult to observe in a typical experimental manipulation; therefore, the necessity to crosscheck every observation and recording of activity during experiments, analysis and interpretation of results from the procedure. Mainly, some suggestions for future research were stated: There are different tests to measure different kinds of pain. It is important to specify the kind of pain to measure and focus the research on drug of choice's ability to eliminate or moderately reduce sensitivity to that particular pain. In which case, using variety of pain measurement options so as to properly evaluate anti-nociceptive effect of drug in all verification is utmost. As there is different rats’ strain, to truly say that cannabis has a significant effect on memory, researches should be done on the different strains and sex, as well as MRI scans to validate results.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: Special thanks to members and staff of Animal House Unit Laboratory, Department of Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom state for providing the researchers with the needed environment and some apparatus to conveniently conduct this experimental study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration:\u0026nbsp;\u003c/strong\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for the research from any institution or individual.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimal ethics\u003c/strong\u003e \u003cstrong\u003eand guidelines\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrinciples of Laboratory animal care” (NIH publication No. 85-23, revised 1985) were followed. All experiments was examined and approved by the Ethics Committee, Department of Psychology, University of Uyo, Akwa Ibom state after proper scrutiny;\u0026nbsp;whereasthe National Drug Law Enforcement Agency (NDLEA), Uyo, Akwa-Ibom State Command with ref no. UU/FSS/D/30/VOL.I (2021) approved the experimental use of cannabis by researchers solely for this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present experimental study on albino wistar rats (vertebrates) complied with the Basel Declarations of 2010 which amongst other things includes greater transparency, trust and communication in the use of animals in experimental studies in addition to the 3Rs (i.e., Reduction, Refinement, and Replacement) in animal research. Further, at the end of the study, and as an acceptable method, sodium pentobarbital was administered via intraperitoneal injection, as the euthanasia agent due to its tolerance level of carbon dioxide exposure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number:\u003c/strong\u003e Clinical trial number: not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAbelev S, Warne LN, Benson M, Hardy M, Nayee S, Barlow J. Medicinal cannabis for the treatment of chronic refractory pain: An investigation of the adverse event profile and health-related quality of life impact of an oral formulation. 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Geneva: World Health Organization; 1997. p. 46.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cannabis and dependency, dose and sex, memory, stimuli and pain sensitivity, albino rats, projective experiment","lastPublishedDoi":"10.21203/rs.3.rs-6512894/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6512894/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe complex and subjective experience of pain makes it a never ending and controversial field for researchers. Apart from the growing body of clinical studies, a history of anecdotal evidence support the use of cannabis for pain relief and memory enhancement across the world, But the drug has been found to also significantly impair memory and other cognitive functions. Based on this, the study experimentally investigated whether cannabis can reduce pain sensitivity, its impact on memory and to determine its sex-dependent effects. The study was carried out at the University of XXX, XXXXXXX. A total of twelve (12) Albino rats were investigated in a pretest, post-test design. The experimental material/instruments include plant materials, novel object recognition test and hot plate apparatus. Using IBM SPSS Statistics and Microsoft Excel, descriptive statistics, one-way within subjects repeated measures ANOVA, and paired sample t-test were employed. Two hypotheses guided this study; and findings showed that effects of cannabis on pain sensitivity were sex-dependent and exposure to cannabis use demonstrated a higher pain tolerance; while rats exposed to cannabis showed more effect on male memory than on female memory. The study therefore concluded that cannabis extract revealed significant sex-dependent and dose-dependent effect on pain sensitivity and memory which can be replicated in humans.\u003c/p\u003e","manuscriptTitle":"Experimental Effects of Cannabis on Pain Sensitivity and Memory: A Scoping Projective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-18 08:22:59","doi":"10.21203/rs.3.rs-6512894/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eedf4205-f7ea-450e-b280-9309da15290d","owner":[],"postedDate":"June 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-12T08:54:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-18 08:22:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6512894","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6512894","identity":"rs-6512894","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}