For some people, marijuana causes a rewarding high.
For others, it produces serious psychiatric side effects.
Whether a person enjoys the experience or adverse effects from cannabis may well be decided by which region of the brain it’s acting upon, Western researchers have determined.
The psychological effects of marijuana can differ between individuals: some experience highly rewarding effects which may lead to dependence on the drug, while others may experience paranoia, cognitive problems or an increased risk of developing schizophrenia.
“Until now, it was unknown which specific regions of the brain were responsible for these highly divergent effects of marijuana,” said Steven Laviolette Ph.D., Professor at Western’s Schulich School of Medicine & Dentistry.
“Translational rodent research performed in our lab has identified highly specific target regions in the brain that seem to independently control the rewarding, addictive properties of marijuana versus the negative psychiatric side-effects associated with its use.”
The study, led by Laviolette and postdoctoral fellow, Christopher Norris, Ph.D., is newly published in Scientific Reports and reveals critical new insights into how marijuana can produce such highly diverse psychological effects in different individuals.
By looking at THC’s effect on a rat brain, the researchers showed that THC, the main psychoactive compound in marijuana, can produce highly rewarding effects in the front-most part of a region of the brain called the nucleus accumbens.
The study showed that THC in this brain area not only produced highly rewarding effects in and of itself, it amplified the addictive properties of opioid drugs like morphine and increased reward-related activity patterns in the neurons.
By contrast, THC in the posterior area of the nucleus accumbens region produced highly adverse effects.
These included more schizophrenia-related cognitive and emotional symptoms and patterns of neuron activity similar to those found in people with schizophrenia.
“These findings are important because they suggest why some people have a very positive experience with marijuana when others have a very negative experience,” said Norris.
“Our data indicate that because the reward and aversion are produced by anatomically distinct areas, the different effects between individuals is likely due to genetic variation leading to differential sensitivity of each area.”
“Marijuana” refers to the dried leaves of the Cannabis sativa plant.1 Internationally, it is the most widely used illicit substance.2
About 2.5% of the world’s population uses marijuana, and it accounts for half of all drug seizures worldwide.2,3
In Canada, the rate of past-month marijuana use is about 10.5%.2
Users report feelings of excitement, euphoria, sensory distortion, sedation or drowsiness from using marijuana,4 which impel usage for similar reasons as alcohol, tobacco and other illicit substances. However, there are negative health effects associated with marijuana use.
Currently, marijuana is legal in 8 US states, Washington and Uruguay, with several other jurisdictions nationally and internationally actively developing legislation.
Canada has legalization currently under consideration at the House of Commons, with legalization having already being considered once by the Senate; legalization is likely to occur by fall 2018.
A broad understanding of the harms associated with marijuana use is needed to inform the clinical community and public, and to support evidence-informed public policy development.
The individual health risks associated with marijuana use are widely reported in several focused systematic reviews.5–7
Syntheses have reported adverse events associated with medical use, the risks associated with use during pregnancy and the association of recreational use with impaired driving.8–11
A recent synthesis from the National Academies of Sciences, Engineering and Medicine included a variety of health effects associated with marijuana, but owing to the heterogeneity of the literature, and time constraints, the report’s breadth was limited to priorities.12
To date, there has been no complete picture of harms and risks published in the peer-reviewed literature.
The objective of this work was to synthesize comprehensively the evidence of the health effects and harms (e.g., mortality, mental health outcomes, respiratory illnesses and cardiovascular diseases) of nonmedical marijuana use within a general population, providing clinicians with a broad and comprehensive overview of possible health impacts.
Owing to the broad nature of this review, we build on the robust existing synthesis literature; thus, we included systematic reviews.
Any systematic review that reported on nonmedical use of cannabis within a population, included any study designs, and assessed any health effect or harm except a therapeutic outcome was included.
This review is intentionally broad on the outcomes included to ensure that we captured the breadth of knowledge available.
Methods
We searched MEDLINE, The Cochrane Database of Systematic Reviews, Embase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, and the Health Technology Assessment Database from the inception of each database to May 2018. Given that systematic reviews evaluating one or other specific harm have been published, this is an overview review with the primary objective of assessing a health effect or harm. Data on author, country and year of publication, search strategy and results, and outcomes were extracted. Quality was assessed using the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist.
Results
The final analysis included 68 reviews. Evidence of harm was reported in 62 reviews for several mental health disorders, brain changes, cognitive outcomes, pregnancy outcomes and testicular cancer. Inconclusive evidence was found for 20 outcomes (some mental health outcomes, other types of cancers and all-cause mortality). No evidence of harm was reported for 6 outcomes.
Interpretation
Harm was associated with most outcomes assessed. These results should be viewed with concern by physicians and policy-makers given the prevalence of use, the persistent reporting of a lack of recognition of marijuana as a possibly harmful substance and the emerging context of legalization for recreational use.
More information: Christopher Norris et al. The Bivalent Rewarding and Aversive properties of Δ9-tetrahydrocannabinol are Mediated Through Dissociable Opioid Receptor Substrates and Neuronal Modulation Mechanisms in Distinct Striatal Sub-Regions, Scientific Reports (2019). DOI: 10.1038/s41598-019-46215-7
Journal information: Scientific Reports
Provided by University of Western Ontario
