Is it the Ideal Time to Start Prescribing Cannabis Derivatives to Treat Endometriosis-associated Pain?

and the reproducibility of findings are limited. 21 Nevertheless, similar findings have been reported in other longitudinal studies. 22 However, at least two meta-analyses focusing on different types of pain 23,24 clarified the limita- tion of the methodological designs available thus far. Fur- thermore, they raised a legitimate concern about the significantly higher prevalence of the adverse effects on the nervous system and psychiatric disorders associated with THC use, 24 particularly including psychosis, depressive episodes, and cognitive alterations commonly. More speci fi- cally, regarding the treatment of endometriosis-associated pain, two clinical trials registered on the clinicaltrials.gov platform (NCT03875261 and NCT04527003) were retrospec - tively proposed by researchers from Barcelona and Pennsyl- vania to assess the effect of cannabinoids on hyperalgesia in women with deep endometriosis, yet both are currently “not yet recruiting. ” To the best of our knowledge, in Brazil, we already have a clinical trial in progress and another that will soon start recruiting and is under our responsibility. Considering the popular saying that “not everything that glitters is gold ” there has been a growing concern in the specialized scientific community regarding the increasingly frequent use ofcannabisor its derivatives for pain relief, despite the potential adverse effects, the lack of robust evidence on benefits and, consequently, the absence of clear recommenda- tions on doses and/or composition to be used. In 2021 the International Association for the Study of Pain (IASP) published a statement position 25 recognizing the legitimacy of the life experience of people who report an improvement in pain following the use of cannabis and cannabinoids. Nevertheless, the association made it explicit that it does not endorse the use of cannabinoids until rigorous investigations and robust results clearly show the benefits and harms of its use in humans. The PAIN journal has even allocated an entire collection of 13 scientific articles representing the IASP ’s Presidential Task Force on Cannabis and Cannabinoid Analgesia and calling for high-quality clinical trials to be initiated. Some of the concerns regarding the use of cannabinoids are potential reductions in neurocognitive performance, macrostructural and microstruc - tural brain development, and alterations in brain function secondary to heavy use by adolescents, 26 who have a higher risk of early onset psychosis,27 and addiction.28 In Brazil, cannabinoid-based medications are of ficially approved for use only in patients with refractory epilepsy with a THC concentration <0.2%. These drugs have a very high cost and any use outside the approved indication is off- label. In any case, we have seen a growing supply ofcannabis- derived products on the market linked to the promise of pain relief. Many serious groups and companies have devoted efforts to drug development, but international quality stand- ards are not followed by all, which poses a health risk as it is impossible to guarantee a high level of quality, adequate pharmacovigilance, and extensive monitoring of adverse reactions. This can also lead to abusive and illegal use. Nevertheless, the prospect of good results is an encour- agement to women with persistent symptoms and profes- sionals who assist them to use cannabinoids, but it is necessary to be aware of the temptation of the premature clinical use of medication. Unfortunately, from a strictly medical and scientific point of view, it is currently impossible to guarantee the ef ficacy, safety and tolerability of cannabis or its derivatives in the treatment of pain symptoms in women with endometriosis. Incentives have been made to disseminate the need for large clinical trials in this domain. To finish, I will restate a part of a text written by Michael Eisenstein 29 which seems to me to be very lucid, sensible and relevant for the situation that we are currently living in: “Unfortunately, if studies such as these are not done —or not done properly —then consumers will be left to fend for themselves in a poorly monitored marketplace. In that scenario, the signal of true clinical bene fit would almost certainly be drowned out by the noise from personal anec - dotes and the placebo effect, which could jeopardize the future of a potentially valuable medicine. ”29 Conflicts to Interest None to declare. Acknowledgments We acknowledge the Coordination for the Improvement of Higher Education Personnel (CAPES) for supporting our post-graduate program. We would like to thank Editage (www.editage.com) for English language editing.

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