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

I’ve watched enough episodes of House, M.D. (and it doesn’t take many) to know that when Dr. Gregory House and his medical team try to nail down each episode’s tricky medical condition, they often suggest a diagnosis of lupus along the way to the right answer.

I’m not unashamed to admit that until recently I couldn’t actually answer the question, “What is lupus?”…. Can you?

Don’t feel bad if you can’t; no one really knows what lupus is, because no one knows what causes lupus. In a nutshell, if you have lupus, it means your immune system has started attacking you — the very thing your immune system is meant to protect. It’s not known why the immune system starts doing this, but once it does, the condition is chronic and any part of your body can be targeted (kidneys, skin, hip joint, you name it).

Who gets lupus? Of the roughly 5 million people in the world with a form of lupus, most of them are women, and Blacks are more susceptible than Whites. You can’t catch lupus from anyone, and the best guess of how one ends up with lupus is through an inherited genetic predisposition (lupus sometimes occurs within families) that turns into full-blown disease after exposure to some environmental factor. A popular metaphor for this disease pattern is, “genes load the gun and environment pulls the trigger.”

Image Source: Color Atlas of Pediatric Dermatology Samuel Weinberg, Neil S. Prose, Leonard Kristal Copyright 2008, 1998, 1990, 1975, by the McGraw-Hill Companies, Inc. All rights reserved.

Because lupus can affect the entire body, symptoms of lupus are wide and varied. Rashes, such as the one at left, are common when the skin is attacked, and patients often experience hair loss, fever, joint pain, seizures, and many other complications as well. In fact, the most common cause of death in lupus patients is kidney failure, because kidneys under immune attack become too inflamed to function.

Being diagnosed with lupus simply requires checking off enough boxes of lupus symptoms for a long enough stretch of time to be classified as having the disease. Unfortunately for lupus sufferers, there is no cure for the disease, and attacking the problem — the immune system — would mean making the patient vulnerable to a whole host of opportunistic infections. Easing pain and preempting complications are currently the field standard.

However, new hope for lupus patients arrived in March of this year, when the FDA approved the first lupus drug to hit the market in 50 years. The drug, belimumab, is an antibody therapy that basically inhibits the factor responsible for B-cells (a type of immune cell) making so many antibodies against the patient. The drug is not perfect, it’s best as part of combination therapy and it has its own side effects, but it’s a definite step in the right direction for effective treatments. It means even scientists are getting better at asking themselves, “What is lupus?”

Espinosa G, & Cervera R (2010). Belimumab, a BLyS-specific inhibitor for the treatment of systemic lupus erythematosus. Drugs of today (Barcelona, Spain : 1998), 46 (12), 891-9 PMID: 21589946

For more on lupus, you can visit http://www.lupus.org and do your own research:

However, despite the benefits of anti-retroviral therapies against AIDS progression, the authors of this paper suggest that these same therapies are associated with the accumulation of mutations in the energy-producing mitochondria of cells — the same kinds of mutations that would naturally occur later in life as part of the aging process.

Title: Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations

Authors: Brendan A. I. Payne, Ian J. Wilson, Charlotte A. Hateley, Rita Horvath, Mauro Santibanez-Koref, David C. Samuels, D. Ashley Price & Patrick F. Chinnery

Date of publication: June 26, 2011

Direct Link: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.863.html

PMID: 21706004

Abstract: In the past few years it has been reported that people who are successfully treated with anti-retroviral therapies against HIV infection show signs of premature aging and ultimately experience progressive multi-organ disease. By performing extensive DNA sequencing and analysis on the single-cell level, these researchers found that patients who had used anti-retroviral drugs had increased mutations in their mitochondria (a cellular subcompartment for generating energy). Because the patients also exhibited premature aging, these results suggest that mitochondrial DNA mutations may play a role in the normal aging process that we all experience.

Methods: The authors obtained frozen muscle biopsy samples from HIV-positive patients treated with or without retroviral drugs and looked for abnormalities in mitochondrial proteins. Also, extremely sensitive sequencing of mitochondrial DNA was used to characterize the mutations in that DNA.

Results: Thirty-three HIV-positive adults under the age of 50 provided muscle biopsies for this work. The authors were looking at a mitochondrial protein that is used by the mitochondria to make energy - the more abnormal the protein, the less healthy the mitochondria. In the patients who had not received anti-retroviral drugs, the amount of this protein, cytochrome c oxidase (COX), was the same as in an HIV-negative control population. However, HIV-positive patients who had received anti-retroviral drugs showed a significant reduction in the amount of COX protein – the protein levels were comparable to or even more reduced than what would be found in the elderly. DNA was analyzed in single cells from these patients and the cells deficient in COX protein showed significantly more deletions in the mitochondrial DNA, including deletions commonly seen in healthy elderly adults (recall, though, that the patients in this research are less than 50-years-old). Also, the total amount of mitochondrial DNA in COX-deficient cells was significantly increased, and the authors propose a theory of “clonal expansion” in these patients: some of the mutated DNA underwent rapid replication, propagating the mutation until a high proportion of the total DNA was mutated.

Bottom line: This research makes two points that I think are highly relevant for disease and health: 1) The knowledge that some anti-retroviral therapies induce a premature aging effect is something that every HIV-positive individual has a right to know before beginning those treatments. Also, now that a potential mechanism has been described for how these drugs may be having an aging effect, researchers have the option to develop combination therapies to stop HIV virus replication while also preventing mitochondrial DNA mutations from accumulating. 2) This work supports the idea that mitochondrial DNA mutations may be part of what causes aging in healthy people, rather than a consequence of the aging process itself.

Payne BA, Wilson IJ, Hateley CA, Horvath R, Santibanez-Koref M, Samuels DC, Price DA, & Chinnery PF (2011). Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nature genetics PMID: 21706004