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European Neuropsychopharmacology (2020) 36, 167–168 www.elsevier.com/locate/euroneuro EDITORIAL Cannabis research: Risks of recreational use and potential medical applications Cannabis sativa derivatives have been used from cen- abundant in specific organs of our body that are crucial turies for recreational and medical purposes. However, the for the control of multiple physiological functions and the discovery of the components of these cannabis derivatives development of several physiopathological processes. CB1 and their mechanism of action have been elucidated only cannabinoid receptors are the most abundant seven trans- in the recent decades. Indeed, the main psychoactive com- membrane domain receptor in the brain and they are crucial ponent of Cannabis sativa, 9–tetrahydrocannabinol, was mediators in the control of multiple central physiological isolated in 1964, by the group of Prof Mechoulam, whereas functions including emotional and cognitive responses, re- the main components of the endocannabionoid system, the warding stimuli, pain, emesis and food intake, among many cannabinoid receptors, their endogenous ligands, and the others (Mechoulam and Parker, 2012). CB2 receptors are enzymes involved in the synthesis and degradation of these abundant in the different tissues of the immune system and endocannabinoids, have been identified in the 80 and 90 are key elements in the regulation of the immune responses decades (Mechoulam and Parker, 2012). (Dhopeshwarkar and Mackie, 2014). The abundance of both Cannabis derivatives represent a major health concern receptors in these two systems and the crucial role that they tacking into account the high prevalence of consumption for play in their physiological control provides unique targets recreational purposes in a large amount of countries world- for therapeutic purposes that have not been yet exploited. wide including North America and European countries. This The activity of these receptors can be modulated by direct recreational use produces major drawbacks in our modern agonists and antagonists, but also through pharmacological societies with particular deleterious consequences in young compounds able to modify the levels of endocannabinoids adolescents that present important prevalence of consump- acting on their synthesis, re-uptake and enzymatic degra- tion starting at early periods of age. Cannabis consump- dation systems. All these tools represent unique opportuni- tion in these early periods may have major long-term con- ties for opening novel therapeutic strategies and research sequences in brains and personalities that are still under on this topic should be promoted to facilitate the possi- a complex developing process of maturation. Large efforts ble development of clinical trials that allow to identify the must be made by scientists, physicians and regulatory au- real therapeutic utility of cannabis components and of other thorities to aware our young citizens about the risks of cannabinoid ligands. cannabis consumption in these early ages. In addition, the Cannabis sativa derivatives are now open to novel chal- pattern of cannabis consumption has been drastically mod- lenges due to the sudden modifications that have already ified in these last months due to the COVID-19 disease that occurred in various countries with regards to the regula- became a global pandemic on March 11th 2020 changing the tion of these substances. It is now obvious that the nega- daily life of our societies and leading to important changes tive health consequences produced by the recreational use in the rate of consumption of cannabis and alcohol, among of cannabis derivatives, including the development of a se- other drugs of abuse. rious disease named cannabis use disorder, cannot be only On the other hand, cannabis derivatives represent phar- fight using prohibitionist measurements. However, the new macological tools of enormous interest in terms of devel- regulations open novel scenarios that must now be closely oping novel possible medications. Indeed, these compounds monitored by the regulatory authorities in order to learn induce their pharmacological effects by acting in two main about the consequences derived and to make the necessary receptors, CB1 and CB2 cannabinoid receptors, that are very https://doi.org/10.1016/j.euroneuro.2020.06.009 0924-977X/© 2020 Published by Elsevier B.V. 168 Editorial efforts in minimizing the negative health costs associated to of (Arranz et al., 2020), investigates sex differences in this consumption. cannabis use and the specific reasons for cannabis use in This Special Issue includes 7 articles that review some of firsts episode of psychosis. These particular topics are al- the most relevant recent basic and clinical research about most unknown at the present moment. On the other hand, the effects of cannabis use and the possible therapeutic ap- the study of (Kredit et al., 2020), elaborates a qualitative plication of cannabinoids. approach to analyze the reasons to explain the increase use In this issue (Lorenzetti et al., 2020), present a review on of medical cannabis for post-traumatic stress disorder. This the possible effects of adolescent and young adult cannabis last study can be specially interesting in the post COVID-19 use on cognitive performance. They present an extensive pandemic where an increase of both post-traumatic stress and complete review of metanalysis and systematics re- disorder and cannabis use are both expected. views of the studies trough neuroimaging tools and neu- We hope that the articles included in this Special Issue ropsychological tests. They also examine prospective epi- provide all together a better understanding of the serious demiological studies on the possible effects of adolescent risks associated to recreational cannabis consumption and and young adult cannabis use on cognitive performance in facilitate the comprehension of the interesting and broad the completion of secondary education and adult life. These therapeutic approaches that may be open in a near future results reveal that cannabis has potential detrimental ef- with the use of cannabinoid ligands. fects on cognition, brain and educational outcomes that References persist beyond acute intoxication, although this impaired cognitive function improves after cannabis abstinence. Dhopeshwarkar, A., Mackie, A., 2014. CB2 Cannabinoid Receptors as a Therapeutic Target—What Does the Future Hold? Mol Phar- The review by (Prini et al., 2020), summarizes the most macol 86, 430–437. relevant findings to explain the neurobiological mecha- Mechoulam, R., Parker, L., 2012. The endocannabinoid system and nisms responsible for these detrimental cognitive effects brain. Annu Rev Psychol 64, 1–27. of cannabis. Cognitive impairments are major drawbacks in Lorenzetti, V., Hoch, E., Hall, W., 2020. Adolescent cannabis use, the recreational use of cannabis, but also may represent cognition, brain health and educational outcomes: A review of an important limitation for the medical use of these com- the evidence. short 36, 169–180. pounds. Both, imaging human studies evaluating brain struc- Prini, P., Zamberletti, E., Manenti, C., Gabaglio, M., Paro- ture and function, and animal models that establish causal laro, D., Rubino, T., 2020. Neurobiological mechanisms under- relationships between these mechanisms and the memory lying cannabis-induced memory impairment. short 36, 181–190. impairment are discussed in this review. Ramaekers, J.G., Mason, N.L., Theunissen, E.L., 2020. Blunted highs: Pharmacodynamic and behavioral models of cannabis tol- The article of (Ramaekers et al., 2020), reviews previous erance. short 36, 191–205. findings that explain the pharmacodinamic mechanisms un- Babalonis, S., Walsh, S. L., 2020. Therapeutic potential of opi- derlying the development of tolerance to the pharmacolog- oid/cannabinoid combinations in humans: Review of the evi- ical effects of cannabinoids. The different neuroadaptions dence. short 36, 206–216. occurring during cannabis consumption explain the differ- Fernández-Ruiz, J., Galve-Roperh, I., Sagredo, O., Guzmán, M., ential effects in acute and chronic cannabis users. These 2020. Possible therapeutic applications of cannabis in the neu- changes are also important in the context of cannabis ther- ropsychopharmacology field. short 36, 217–234. apeutics and in legal settings to understand the impact of Arranz, S., Mané, A., Bergé, D., Monserrat, C., cabezas, A., cannabis exposure on human function. Vilella, E., Sanchez-Gistau, V., 2020. The impact of sex and Another hot topic, the use of cannabis and cannabinoids cannabis on clinical features in first–admitted patients with psy- chosis. short 36, 235–243. to replace opioid analgesics or to reduce opioid use has been Krediet, E., Janssen, D. GA, Heerdink, E. R., Egberts, T. CG, Ver- targeted by (Babalonis et al., 2020). The authors review the metten, E., 2020. Experiences with medical cannabis in the main scientific evidence from basic and clinical studies. This treatment of veterans with PTSD: Results from a focus group review stresses the limited controlled evidence now avail- discussion. short 36, 244–254. able, and the often negative findings reported on the ther- apeutic co-use of opioid and cannabinoid agonists. The possible therapeutic applications of cannabis and Rafael Maldonado cannabinoids in the neuropsychopharmacology field has Laboratory of Neuropharmacology, Department of been revised by (Fernandez-Ruiz et al., 2020). The au- Experimental and Health Sciences, Universitat Pompeu thors provide a review of the basic and clinical evidence Fabra, PRBB, c/ Dr. Aiguader, 88, 08003 Barcelona, Spain supporting the cannabis-based therapies for different dis- IMIM (Hospital del Mar Medical Research Institute), PRBB, eases of the central nervous system. The role of cannabis c/ Dr. Aiguader, 88, 08003 Barcelona. Spain and cannabinoids in different aspects of the treatment of schizophrenia and related psychoses, mood and anx- Marta Torrens iety disorders, drug addiction, sleep disorders, epilepsy, IMIM (Hospital del Mar Medical Research Institute), PRBB, post-traumatic stress disorder, anorexia nervosa, dementia, c/ Dr. Aiguader, 88, 08003 Barcelona. Spain autism and neurodevelopment diseases is discussed. Institut de Neuropsiquiatria i Addiccions, Hospital del Finally, a classical question is reviewed in two of the Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain articles included in this Issue, i.e., why do people with Psychiatry Department, Universitat Autònoma de some psychiatric disorders use so often cannabis? The study Barcelona (UAB), Cerdanyola del Vallès, Spain