marijuana adverse effects review nejm2014

there have been several concerning studies about the adverse effects of marijuana, of increasing importance now as legalization becomes more of an issue (which is not to say that other legal substances, such as alcohol or cigarettes, are better than marijuana. just that there are several newer studies showing that adverse effects of marijuana are more impressive than was understood before, and, with more widespread access, may lead to significant morbidity). in addition, the potency of marijuana has increased dramatically (THC content in 1980s of 3%, now it's 12%). the natl institute on drug abuse (NIDA), a division of NIH, just published an overall review (see marijuana adverse effects review nejm2014 in dropbox, or DOI: 10.1056/NEJMra1402309).   findings:

short-term effects:

    --impaired short-term memory, making it difficult to learn and retain information

    --impaired motor coordination, increasing risk of injury (esp motor vehicular). relationship between blood THC levels and performance in driving-simulation studies. more car accidents if use marijuana, but alcohol is worse.

    --altered judgment, esp increase in high-risk sexual behaviors

    --paranoia and psychosis, esp with higher doses

long-term effects:

    --risk of addiction: approx 9% of users become addicted (per DSM-IV criteria), increasing to 1 in 6 in those who start as teenager and to 25-50% of those who smoke daily (2.7 million people in US over age 12 meet criteria for addiction, and 8.6 million meet addiction criteria for alcohol). withdrawal symptoms include irritability, sleeping difficulties, dysphoria, craving, anxiety. in general, adolescents seem to be more susceptible to adverse long-term effects, perhaps because the brain, including the endocannabinoid system, is actively developing in adolescence. cannabinoid dependence is 2-4 times more likely if begin marijuana as adolescent vs adult.

    --brain development: brain is actively developing until around age 21. adults who smoked marijuana regularly as adolescents have fewer neural connections in specific brain regions, including the precuneus (a node involved in higher integration functions, such as alertness and self-conscious awareness), the fimbria (part of hippocampus important for learning and memory), prefrontal networks (for executive function), and subcortical networks (which process habits and routines). and, not surprisingly, frequent findings of decreased IQ in frequent users. also, poorer educational outcomes and increased likelihood of dropping out of school.

    --??gateway drug: unclear if marijuana use leads to other drug use, or if those inclined to drug use just start with marijuana (cheap, accessible). but, some of the animal studies are concerning: those exposed to marijuana when young have alterations in their mesolimbic dopamine reward systems, which can prime the brain for enhanced responses to other drugs

    --relation to mental illness: some data that there is increase in psychosis, esp in those with genetic predisposition, though hard to establish causality. heavy use associated with earlier first psychotic episode than otherwise expected.

    --cancer: lung cancer possibly associated, but nowhere near level of cigarettes. seems to be more chronic bronchitis (and inflammation of large airways, increased airway resistance, lung hyperinflation) in chronic marijuana smokers. some increase in respiratory infections and pneumonia. ??association with vascular disease (MI, stroke), with noted acute changes in vascular resistance and coronary microcirculation.

positive effects (ie, the rationale for medicinal marijuana):

    --stimulate appetite, esp in those with AIDS (though there are some data that marijuana could exacerbate HIV-associated cognitive deficits)

    --combating nausea/vomiting, esp in those on chemotherapy

    --helping relieve severe pain and some types of spasticity

    --decreasing intraocular pressure in those with glaucoma

    --anti-inflammatory effects -- ??role in IBD or rheumatoid arthritis (some data on cannabidol, which is devoid of psychoactive effects)

    --MS -- some efficacy for neuropathic pain, sleep disturbance, and spasticity

so, the brain effects are particularly concerning. also, the old mantra that marijuana is non-addicting seems to be wrong. at the health center, we are certainly seeing lots of patients, adolescents but also 70 year olds, smoking marijuana regularly. a few are able to decrease or stop just by engaging them in discussion (more so, in my experience, in adults than teens). others may benefit from psychosocial support, including cognitive behavioral therapy and motivational interviewing.