The very recent publication of a draft of the Cannabis sativa genome has inspired me to briefly review why it’s so hard to do research on weed, and to highlight studies that have shown the benefits that can come from considering marijuana as more than just an abused substance.

Some would say our brains were made for marijuana, or vice versa, because of the abundant cannabinoid receptors that are directly activated by the primary psychoactive chemical in marijuana — a cannabinoid called delta-9-tetrahydrocannabinol (THC). The human body even produces its own endocannabinoids, which activate the same cannabinoid receptors. These receptors are known to have a role in everything from pain sensation to mood to appetite, and more, with some functions perhaps yet to be discovered.

 But about that medical research: much of what’s difficult in drug trials is establishing how toxic the test drug is and what its side effects are. Well, I think it’s generally accepted that there’s no documented human fatality from THC overdose, and as for side effects…well, just watch any one of the myriad “stoner movies” out there (e.g. 1, 2, 3, 4, 5, 6, 7, and 8). Many of the side effects are known quite well.

So what’s the big deal? Well, it all comes down to the fact that the Drug Enforcement Agency (DEA) classifies marijuana as a Schedule 1 drug, where it joins such baddies as heroin, LSD, and ecstasy. Schedule 1 drugs are defined as those that “have no currently accepted medical use in treatment in the United States.” The fact that marijuana is listed among these drugs can be perplexing, what with medical marijuana being legal in at least 16 states and our nation’s capitol.

"No medical use"? Let science decide.

So let’s say you’re a medical researcher, and you want to study the efficacy of marijuana in treating disease X; here are the three hurdles you have to jump: 1) applying for and receiving a license from the DEA, who fears Schedule 1 drugs getting into the wrong hands; 2) getting express approval from your research institution, who just might not want the stigma that comes with your research; and 3) securing funding, which, for Schedule 1 drugs, mostly comes from the National Institute on Drug Abuse (NIDA). NIDA has a government-sanctioned monopoly as the only legal source of marijuana for research in the U.S., and word on the street is that they don’t like to fund research that could conflict with their interest in, well, drug abuse.

To make a long story short, the debate over legalizing marijuana for medical research has a lot to it. Even if this legalization did occur, there would need to be firm oversight to make sure everyone and their mom didn’t run to sign up for studies just to get some reefer. But, in hopes of tilting the balance of this plant’s reputation, I am featuring a list of research studies in which THC, marijuana’s main active compound, appears to have done some good:

1. Cannabinoid Neuroimmune Modulation of SIV Disease. Monkeys with simian immunodeficiency virus (SIV, the monkey version of HIV) were given THC and experienced slowed disease progression, decreased amounts of virus, and milder tissue inflammation.

2. Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats. THC protected rats from ecstasy-induced hyperthermia and neurotoxicity, as well as prevented ecstasy’s behavioral effects.

3. Cannabinoids mediate opposing effects on inflammation-induced intestinal permeability. In inflammatory bowl diseases (IBD) like Crohn’s disease and ulcerative colitis, the intestines are inflamed; in this study, THC accelerated recovery from induced inflammation in human colorectal cells.

4. Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington’s disease. A THC-based treatment delayed the progression of Huntington’s Disease in rats.

5. Targeting cannabinoid receptors as a novel approach in the treatment of graft-versus-host disease: evidence from an experimental murine model. Mice with graft-versus-host disease were given THC and had increased numbers of immune cells, less tissue injury, less weight loss, and better overall survival.

6. Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. THC reduced the viability of human hepatocellular carcinoma (liver cancer) cells and of tumors grown from human cancer cells implanted in mice.

7. The cannabinoid receptor agonist THC attenuates weight loss in a rodent model of activity-based anorexia. THC caused anorexic rats to gain weight.

8. Pre- and post-conditioning treatment with an ultra-low dose of Δ9-tetrahydrocannabinol (THC) protects against pentylenetetrazole (PTZ)-induced cognitive damage. Mice given THC before or after induced epilepsy (a model of brain injury) were protected from long-lasting deficits in learning and memory.

9. A combined preclinical therapy of cannabinoids and temozolomide against glioma. THC had anti-tumor effects against gliomas (brain tumors) that were resistant to temozolomide, the standard treatment for gliomas; the gliomas in the studies were grown by implanting human glioma cells in mice.

10. Acute and chronic cannabinoid extracts administration affects motor function in a CREAE model of multiple sclerosis. In a mouse model of multiple sclerosis, injection with a THC-rich Cannabis sativa extract reduced neurological deficits.

…And that’s all just from this year.

van Bakel H, Stout JM, Cote AG, Tallon CM, Sharpe AG, Hughes TR, & Page JE (2011). The draft genome and transcriptome of Cannabis sativa. Genome biology, 12 (10) PMID: 22014239

But what does the research say?

The more obvious benefits of laughter are that it relaxes you, it’s aerobic and gets your blood moving, and it can really work your abs. What interests me the most, however, is the ability of laughter to significantly lower the body’s level of cortisol. Cortisol is a hormone that the body produces in response to stress, and while I’m sure it was extremely useful back in the early human days when stress meant encountering a bear or not finding food for days, people today can find themselves stressed when there’s no Wi-Fi or if their order gets messed up at a restaurant. This isn’t to say that there aren’t legitimate reasons to be stressed in today’s society, but we could all probably use a way to lower our cortisol levels. This is especially true considering that cortisol is known to suppress the immune system, increase blood pressure, act as a diuretic, and have other effects you might not need just because you can’t find your car keys. So, maybe the link between laughter and lowered cortisol helps to explain the research findings below, but regardless, laughter seems like pretty awesome stuff:

1. Laughter and cancer. Last year, researchers in Japan prescribed laughter therapy to an 88-year-old woman with advanced stomach cancer. She didn’t want traditional cancer treatments, so for a year and seven months the team responsible for her care focused instead on making her feel safe and relaxed and “increasing her joy of living.” At the end of her laughter therapy, a biopsy showed that the molecular features of her cancer had improved and the classification of her tumors were of a less severe type than before. Even five years afterwards she was still in “good condition”; the five-year survival rate for her type of cancer is 45%. Even though this one woman is an extremely small sample size, if she truly did only laugh more and feel more positively as her only treatment, then I am duly impressed.

2. Laughter and IVF. Doctors in Israel working with women seeking in vitro fertilization wanted to test whether stress reduction could improve fertility, so they arranged an experiment to do so. Out of 219 women, 110 were visited by a professional medical clown for 12-15 minutes immediately after their embryos were implanted, and the other 109 were not. Ultimately, 36.4% of the women who got the clown treatment became pregnant, compared to only 20.2% of the control group (this was very statistically significant, p=0.008). Maybe Israel has the right idea in offering degrees in medical clowning.

3. Laughter and immune function. This study in California supports the idea that if cortisol suppresses the immune system and laughter suppress cortisol, then laughing should improve our immune responses. In a group of 52 men, a subset watched a 1-hour “humor video” and an equal number did not. Before and after the viewing, blood samples were taken from the study participants. Significant increases were seen in immune cell activity (natural killer cells, B cells, helper T cells, and others) and the amount of circulating antibodies in the men who watched the video compared to those who hadn’t. This study was not the only one to observe these immune effects of laughter.

Doing a search for the research on laughter therapy will reveal many more applications of the biological benefits of laughter than the few I’ve shown here. I really can’t emphasize this enough: even if you’re still skeptical, laughing is still one of the simplest, most cost effective methods to potentially help yourself — what’s to lose by trying? And while I’m sure that few people are opposed to laughing as it is, you can make actual conscious efforts to laugh more in your life, like joining the laughter yoga movement.

To help get you started, I’ve never known anyone to watch this video and not laugh — do it for your health!

Noji S, & Takayanagi K (2010). A case of laughter therapy that helped improve advanced gastric cancer. Japan-hospitals : the journal of the Japan Hospital Association (29), 59-64 PMID: 21706962
 
Friedler S, Glasser S, Azani L, Freedman LS, Raziel A, Strassburger D, Ron-El R, & Lerner-Geva L (2011). The effect of medical clowning on pregnancy rates after in vitro fertilization and embryo transfer. Fertility and sterility, 95 (6), 2127-30 PMID: 21211796
 
Berk LS, Felten DL, Tan SA, Bittman BB, & Westengard J (2001). Modulation of neuroimmune parameters during the eustress of humor-associated mirthful laughter. Alternative therapies in health and medicine, 7 (2) PMID: 11253418