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Does Cannabis Consumption Negatively Affect Cognition? a Review of the Scientific Evidence ASEAN Journal of Psychiatry, Vol

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Does Cannabis Consumption Negatively Affect Cognition? a Review of the Scientific Evidence ASEAN Journal of Psychiatry, Vol Does Cannabis Consumption Negatively Affect Cognition? A Review Of The Scientific Evidence ASEAN Journal of Psychiatry, Vol. 18 (2), July - December 2017: XX-XX REVIEW ARTICLE DOES CANNABIS CONSUMPTION NEGATIVELY AFFECT COGNITION? A REVIEW OF THE SCIENTIFIC EVIDENCE Attilio Rapisarda*, **, ***, Keane Lim*, Jimmy Lee*, ^ *Research Division, Institute of Mental Health, 10 Buangkok View Singapore 539747; **Medical Education, Research & Evaluation Department, Duke-NUS Medical School, 169857 Singapore;***Program in Neuroscience & Behavioral Disorders, Duke-NUS Medical School, 169857 Singapore; ^Department of General Psychiatry 1, Institute of Mental Health, 10 Buangkok View, Singapore 539747. Abstract Objective: This review summarises the existing evidence on the effects that recreational and medical use of cannabis and cannabinoids have on cognitive performance. Methods: Databases (PubMed, Medline, and Google Scholar) were searched from inception to March 2017 by adopting the following key terms: dronabinol, nabilone, nabiximols, cannabis, marijuana, cognition, neurology, and neuropsychology. A total of 94 documents, including reviews, preclinical and clinical studies, industrial and government agencies reports were included in this review. Results: We found that recreational use of cannabis doubles the risk of a fatal traffic accident by impairing attention and lengthening reaction time. Short-term use lowers performance in working memory, attention, executive functions and visual perception tasks. Chronic recreational use in adolescents also doubles the risk of early school-leaving, cognitive impairment and psychoses in adulthood. Adverse effects of cannabis-based medication – dronabinol, nabiximol and nabilone – and ingestion/inhalation of marijuana allowed for medical use include dizziness, drowsiness and short-term memory impairment. Conclusion: Cannabis consumption is associated with significant impairments in a range of cognitive abilities. Of particular concern, early and chronic exposure to cannabis, especially in the adolescence, seems to be associated with irreversible cognitive impairments. ASEAN Journal of Psychiatry, Vol. 18 (2): July – December 2017: XX XX. Keywords: Cannabis, Cannabinoids, Cognition, Neuropsychology Introduction reference to three different classes of active compounds that exhibit effects, especially in “Cannabis” is frequently adopted in reference the central nervous system (CNS) and immune to the flowering tops of the female Cannabis system: (i) phytocannabinoids, which are the sativa plant. Cannabis is usually smoked or constituents of Cannabis sativa and include, ingested to achieve the desired psychoactive among others, THC and CBD, (ii) effects of euphoria and increase sociability. endocannabinoids, which act as Such effects are primarily produced by delta- neuromodulators and neurotransmitters in the 9-tetrahydrocannabinol (THC) and are human body and (iii) synthetic cannabinoid modulated by cannabidiol (CBD), a non- preparations, of which three are currently psychoactive cannabinoid [1]. The more approved for medical use – dronabinol general term “cannabinoids” is used in (Marinol), nabiximol (Sativex) and nabilone Does Cannabis Consumption Negatively Affect Cognition? A Review Of The Scientific Evidence ASEAN Journal of Psychiatry, Vol. 18 (2), July - December 2017: XX-XX (Cesamet) – and seven are still under immune [19] and stress responses [20], control development by the pharmaceutical industry: energy balance [21], promote sleep [22] and dexanabinol, CT-3, cannabinor, HU 308, HU lower spasticity associated to multiple 331, rimonabant, taranabant [2, 3]. sclerosis [23]. This review collects the evidence on the cognitive risk associated with Phytocannabinoids and synthetic cannabinoids the early, short-term and long-term assumption are used in medicine to ease chemotherapy- of cannabis for medical and/or recreational related nausea and vomiting, chronic pain, reasons. neuropathic pain, muscle spasm, anxiety and sleep disturbances. Other proposed medical Methods use include anti-inflammatory activity, antiviral activity and antitumoral activity [4]. Types of Studies Endocannabinoids are a class of bio-active lipids that serve as natural ligands of the Randomized clinical trials (RCTs) comparing cannabinoid receptors. Anandamide (N- cannabinoids with usual care, placebo or no arachidonylethanolamide, AEA) was the first treatment in various patient populations were of such ligands to be isolated, in 1992, included in this review. Non-randomized, non- followed by 2-arachidonoylglycerol (2-AG) controlled studies were also reviewed when [5]. More recently, three more including at least 25 participants. In vitro, in endocannabinoids were identified: 2- silico and animal studies on endocannabinoids arachidonyl-gliceryl-ether (noladin, 2-AGE) signalling and endocannabinoids receptors [6], virodhamine (O-arachidonyl were also included when pertinent to explore ethanolamine) [7] and N-arachidonyl the effects of suppression/enhancement on dopamine (NADA) [8]. cognition. Endocannabinoids are synthesized in the post- In addition, scientific literature reviews, synaptic terminals of neural cells and bind to industry reports and government reports on the the cannabinoid receptors in near-by cells or in adverse effects of cannabis on cognition in the same cells that synthesized them [9]. The patients and healthy individuals who reported two most relevant receptors for cannabinoids recreational use of cannabis were reviewed. are the CB1 and CB2, predominantly expressed Any anecdotal literature, which was prevalent in the Central Neural System (CNS) and in Google Scholar searches, was excluded immune system respectively [10]. Once from the review. released, endocannabinoids are inactivated via reuptake, hydrolysis or absorbed within the Types of Participants phospholipidic layers of the cellular membrane [11]. Endocannabinoids serve as a Studies with participants of any age and neuromodulator system that controls neural gender consuming cannabis in any of the excitability by either initiating a second following situations were included: (i) messenger cascade reaction or by interacting chemotherapy-induced nausea and vomiting; with gamma-aminobutyric acid-ergic (GABA- (ii) appetite stimulation in HIV/AIDS, (iii) ergic), serotoninergic, glutamatergic or chronic pain, (iv) spasticity due to multiple dopaminergic transmission [12]. sclerosis (MS) or paraplegia, (v) depression, (vi) anxiety disorders, (vii) post-traumatic The physiological role of the stress disorder, (viii) sleep disorders, (ix) endocannabinoids system is very diverse. It psychosis, (x) intraocular pressure in controls appetite by increasing hunger after glaucoma, and (xi) neurological disorders endocannabinoid binding with the central CB1 (amyotrophic lateral sclerosis, dystonia, receptors in the hypothalamus [13]. It is also Huntington’s disease, Parkinson’s disease, involved in the extinction of old memories by Tourette’s syndrome). suppressing long-term potentiation in the hippocampus[14]. Endocannabinoids also Types of Consumption/Intervention possess antiemetic [15], analgesic [16], anticonvulsive [17], and hypotensive Studies exploring the association between properties [18]. They also seem to modulate cognitive performance and any form of Does Cannabis Consumption Negatively Affect Cognition? A Review Of The Scientific Evidence ASEAN Journal of Psychiatry, Vol. 18 (2), July - December 2017: XX-XX medical or recreational cannabis consumption memory was noted 10 minutes after drug- were included in the review: smoked/ingested administration [34, 35]. phytocannabinoids or administered synthetic cannabinoids. A study comparing psychomotor performance across a group of occasional users and chronic Search Strategy users engaged in a driving simulation task intuitively showed that both users were The literature review was conducted in June significantly impaired compared to non-users 2015 and updated continuously until March but – counter-intuitively – occasional users 2017 using three popular databases: PubMed, were more impaired than chronic users, Medline and Google Scholar. Relevant perhaps as a result of a more cautious literature was generated by using key search behaviour in the chronic users, who were more terms in several different combinations to aware of their level of intoxication [36, 37]. retrieve as many publications as possible. The Recent systematic reviews and meta-analyses comprehensive list of search terms used concluded that acute cannabis use is associated included dronabinol, nabilone, nabiximols, with a two-[3, 38, 39] to seven-fold [40] risk cannabis, marijuana, hashish, cognition, of being involved in a fatal accident. neurology, neuropsychology, prenatal. Acute Exposure to Medical Cannabis and Results Neuropsychological Functioning From the PubMed, Medline and Google The most frequently reported adverse events Scholar database searches a total of 70 reported in clinical trials after acute publications were included to identify trend in administration of dronabinol (Marinol©) and the association between recreational and nabiximols (Sativex©) – drowsiness, dizziness, medical use of cannabisand cognition. It is transient impairment of sensory and perceptual worth noting that “medical use” may include functions [41, 42] – involve the Central the administration of cannabis-derived Nervous System (CNS). These effects were pharmaceutical formulations as well as reported in 24% of patients receiving Marinol© cannabis
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