Monday, May 27, 2013

Can Pot Smoking Counter the Negative Metabolic Consequences of Atypical Antipsychotics?

DISCLAIMER: This is a hypothetical question and not a medical recommendation. But it might be an idea worth investigating in epidemiological studies.

Everyone knows that pot gives you the munchies. So the paradoxical finding that marijuana use is associated with a lower prevalence of obesity and diabetes came as a quite surprise to me. Now, a new study has concluded that pot smokers also have lower fasting insulin levels and smaller waistlines (Penner et al., 2013).

I'll let the authors summarize the clinical significance of their study (Penner et al., 2013):
  • Marijuana use is increasingly common, and use of medical marijuana is now legal in 19 states and the District of Colombia.
  • Despite its associations with increased appetite and caloric intake, marijuana use also is associated with lower body mass index and prevalence of diabetes.
  • In a nationally representative survey population, we found current use of marijuana to be associated with lower levels of fasting insulin, lower insulin resistance (homeostasis model assessment of insulin resistance), and smaller waist circumference.

More complete coverage of this article is available at Addiction Inbox and Time Healthland.

Marijuana Use and Mental Illness

Some other observations that I will attempt to string together:
I will not address the issue of whether cannabis use is a risk factor for psychosis here.1 In fact, all of my observations will be related to the metabolic effects of marijuana and not to its psychoactive properties and possible detrimental effects on mental health.

Although cigarette smoking, alcohol use, unhealthy diet, and lack of exercise may contribute to shorter life expectancy in patients with serious mental illnesses (Lawrence et al., 2013), one has to wonder about the effects of atypicals on physical health.2 These drugs can have a very positive effect on mental health, but it comes at a cost.

  • Interestingly, cannabis use is not associated with greater mortality. In fact, the opposite has been reported by Koola et al. (2012), who "observed a lower mortality risk in cannabis-using psychotic disorder patients compared to cannabis non-users despite subjects having similar symptoms and treatments."
A total of 762 patients with a psychotic disorder were included in that study. All were on atypical antipsychotics, and 39% used marijuana (although this is often under-reported). The authors speculated on the potential health benefits of cannabis, including its anti-inflammatory effects. However, they didn't mention reductions in obesity and diabetes as possible causes of lower mortality in cannabis users. This association bears further investigation, in my view.

  • Nevertheless, eliminating marijuana to counteract the increase in appetite brought on by atypicals seems like common sense. In fact, this has been proposed as a specific behavioral intervention (Werneke et al., 2013).
Those authors assumed that cannabis contributes to the weight gain caused by the prescription medication, which I also assumed (until reading the new papers cited here). But this relationship hasn't really been studied (Werneke et al., 2013):
As the endocannabioid system is linked to increased appetite and cannabioid receptor antagonists can induce weight loss [15] cannabis consumption will most likely potentiate antipsychotic-associated weight gain. As the prevalence of cannabis use in people suffering from psychosis is so high, the contribution of cannabis to weight gain in this population is likely to be significant. Surprisingly, this link between cannabis and weight gain remains largely ignored at present.

We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age. Here, we propose that this effect is directly related to exposure to the Δ9-tetrahydrocannabinol (THC) present in cannabis smoke. We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.
These authors have filed a patent application for 'Use of marihuana and compounds therein for treating obesity' (which they acknowledge in the paper).

  • One of the same authors (Le Foll) has also published on 'Cannabis use and cannabis use disorders among individuals with mental illness' (Lev-Ran et al., 2013), which they found to be particularly high in individuals with Bipolar I disorder (especially in men). 
Many of these bipolar cannabis users are probably on atypical antipsychotics. This information was not reported in the paper, but it might be available in the National Epidemiologic Survey on Alcohol and Related Conditions (although this is not certain).

To be completely clear, I am not advocating the use of marijuana by persons with schizophrenia or bipolar disorder. Rather, I am suggesting that the relationship between atypical antipsychotics and variables such as body mass index, waist circumference, insulin, glucose, and diabetes be compared between groups who do use cannabis vs. those who don't. If there is a benefit in the pot smokers, perhaps there could be a psychiatrically safe, cannabis-derived compound for weight loss in the future. Isn't that more likely than the development of 'third generation' antipsychotics that do not cause substantial weight gain?


1 Interested readers can consult these articles and posts.

2 See also Rising Mortality Rates for People with Serious Mental Illness and Improving the Physical Health of People With Serious Mental Illness.


Green B, Young R, Kavanagh D. (2005) Cannabis use and misuse prevalence among people with psychosis. Br J Psychiatry 187:306-13.

Koola, M., McMahon, R., Wehring, H., Liu, F., Mackowick, K., Warren, K., Feldman, S., Shim, J., Love, R., & Kelly, D. (2012). Alcohol and cannabis use and mortality in people with schizophrenia and related psychotic disorders. Journal of Psychiatric Research, 46 (8), 987-993 DOI: 10.1016/j.jpsychires.2012.04.019

Lawrence D, Hancock KJ, Kisely S (2013). The gap in life expectancy from preventable physical illness in psychiatric patients in Western Australia: retrospective analysis of population based registers. BMJ 2013; 346 (Published 21 May 2013).

Le Foll, B., Trigo, J., Sharkey, K., & Strat, Y. (2013). Cannabis and Δ9-tetrahydrocannabinol (THC) for weight loss? Medical Hypotheses, 80 (5), 564-567 DOI: 10.1016/j.mehy.2013.01.019

Lev-Ran, S., Le Foll, B., McKenzie, K., George, T., & Rehm, J. (2013). Cannabis use and cannabis use disorders among individuals with mental illness, Comprehensive Psychiatry DOI: 10.1016/j.comppsych.2012.12.021

Penner, E., Buettner, H., & Mittleman, M. (2013). The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults. The American Journal of Medicine DOI: 10.1016/j.amjmed.2013.03.002

Werneke U, Taylor D, Sanders TA. (2013). Behavioral interventions for antipsychotic induced appetite changes. Curr Psychiatry Rep. 15(3):347.

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At May 27, 2013 6:35 AM, Anonymous Tetyana said...

Very intriguing! Great post, Neurocritic!

At May 27, 2013 12:10 PM, Blogger The Neurocritic said...

Thanks! It's very counterintuitive, given the use of medical marijuana and cannabis-derived compounds to stimulate appetite (and cause weight gain) in HIV/AIDS and cancer. The Le Foll et al. paper discusses potential differences between acute and chronic THC administration.

At May 27, 2013 4:56 PM, Anonymous Anonymous said...

Good catch! This is definitely worth following up on in research. Let's face it-- having problems with perceiving the world accurately and reasoning about it in a logical manner are bad enough. But if you have to take medicine to help with these problems, and then become fatter than a house, that just adds more misery to your adaptive struggles.

At May 31, 2013 1:40 PM, Anonymous Anonymous said...

There's an irony or something here: pot can be prescribed as medicine, but there's no guidelines for dosage or active product (strains rich in THC v. CBD).

What is the mechanism of action? CNS or peripheral? Metabolic or lower food intake after the acute munchie episode?

At June 27, 2013 3:20 PM, Blogger wblakesx said...

NC- are you using a lit critic mindset/frame?


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