THC for Huntington’s Disease? Cannabinoid receptors are important for more than drug use

Here at A3, we believe in equal opportunity. We recognize that saying we have an addiction problem is not the same as saying we have a drug use problem and that just because some people abuse substances (or belief systems) doesn’t means that these have no actual value when not abused. Enter this recent paper on CB1 receptors, THC, and Huntington’s Disease.

Those of you who haven’t been reading A3 for too long (shame on you!) may not be familiar with my comparison of the cognitive (or mental) impulsivity associated with substance use disordersand the physical “impulsivity” common to Huntington Disease(HD) patients. To make a long story short – both of these dysfunctions have to do with the striatum, a brain area responsible for inhibiting and controlling unwanted brain output (as in thoughts or actions). When this area starts malfunctioning, everything goes awry. When it comes to HD, “goes awry” doesn’t really do the disorder justice. Patients with a progressive form of the condition end up flailing their limbs in a manner that’s been coined the “Huntington Dance,” a euphemism if I ever heard one. This motor flailing is closely followed by severe cognitive impairments and a premature death. Not a pretty story. Continue reading “THC for Huntington’s Disease? Cannabinoid receptors are important for more than drug use”

THC for HIV: Is smoking weed the only way?

The medical marijuana debate is still raging and I have little doubt that it will be around for at least a decade to come. In the mean time, there is little doubt that marijuana, and more specifically its most active ingredient THC, are useful for individuals suffering from a number of medical conditions (see medical uses of marijuana). One of those conditions is HIV, where THC is particularly useful for helping patients fight the anorexia that often goes along with the infection and treatment. While a number of states (15 and the District of Columbia at last count) allow for medical marijuana prescriptions, most others require that patients get their THC in a synthetic form known as dronabinol.

Synthetic THC in a capsule

I’m not getting into the discussion of whether putting THC in a synthetic form is the American government’s way of directing money towards the pharmaceutical industry. The bottom line is that smoking marijuana, like smoking cigarettes, causes pulmonary (as in lung) problems including an increased risk of cancer as well as a host of other diseases like emphysema and such. New(ish) devices like vaporizers may help reduce that risk, but until more data comes in, I doubt those are going to cause any movement in terms of legislation. And since smoking marijuana is still illegal in most states, patients are pretty much left with the dronabinol pill.

The only problem is that something like 30% of HIV patients report smoking marijuana any way for relief of disease-associated symptoms and no one ever assessed the effectiveness of dronabinol on these patients until now. In this recent study, researchers assessed the efficacy of a very high dose of dronabinol (10mg – twice the recommended daily dose and half of the allowed daily maximum dose) on HIV/AIDS patients who smoke marijuana recreationally. Not surprisingly these patients showed a reduced response to the drug and even this high dose was only effective for the first half (eight days – during which they consumed 350 more calories a day and slept better) of the experimental period, after which it was no more effective than placebo at improving caloric intake and sleep.

The researchers’ conclusion in this article is that is seems higher doses are necessary for these patients, although I wonder about the rates of lying about regular marijuana use by patients given its legal status in most states. The patients in this study all smoked marijuana but while some smoked sporadically (2 days a week), others were daily or near daily smokers. I would assume that those two groups reacted differently to the dronabinol, but this paper didn’t address any such differences.

So… Do you have to smoke weed to get the medical benefit of THC?

Overall this study, like a few others before it, shows that synthetic THC is effective in treating a number of the effects of HIV/AIDS infection and treatment. Nevertheless, there is little doubt that HIV patients who use marijuana require different dosing than patients who don’t smoke weed, an effect that was probably predictable. Given the high prevalence of marijuana smoking among HIV/AIDS patients, it seems that more research should be carried out in order to fully develop a recommended dose range for such patients.

For HIV/AIDS patients who live in states where medical marijuana use is legal, it is likely easier and more cost effective to get their THC from marijuana leaves, though given their increased risk of infection and the lung effects of inhaling smoke, they should likely play it safe and use a vaporizer rather using more traditional methods (as in joint, bowl, or bong). The last thing HIV patients need to do is to put their body at any increased risk of any sort of medical complication. However, since dosing can be an issue this way, and since not everyone objects to the notion of taking pills instead of smoking weed, dronabinol might be a good options for those who are simply looking to counteract their infection complications and not to light up.

Citations:

Gillinder Bedi, Richard W. Foltin, Erik W. Gunderson, Judith Rabkin, Carl L. Hart, Sandra D. Comer, Suzanne K. Vosburg & Margaret Haney (2010). Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study. Psychopharmacology, 212, 675-686.

Arno Hazekamp, Renee Ruhaak1, Lineke Zuurman, Joop van Gerven, Rob Verpoorte (2006). Evaluation of a vaporizing device (Volcano®) for the pulmonary administration of tetrahydrocannabinol. Journal of Pharmaceutical Sciences, 95, 1308-1317.

Is marijuana addictive? You can bet your heroin on that!

marijuana“Is marijuana addictive?” seems to be the ultimate question for many people. In fact, when discussing addiction, it is rare that the addiction potential for marijuana doesn’t come up.

Some basic points about marijuana:

The active ingredient in marijuana, THC, binds to cannabinoid receptors in the brain (CB1 and CB2). Since it is a partial agonist, it activates these receptors, though not to their full capacity. The fact that cannabinoid receptors modulate mood, sleep, and appetite is why you get the munchies and feel content and why many people use it to help with sleep.

But how is marijuana addictive? What’s the link to heroin?

What most people don’t know is that there is quite a bit of interaction between the cannabinoid receptor system (especially CB1 receptors) and the opioid receptor system in the brain. In fact, research has shown that without the activation of the µ opioid receptor, THC is no longer rewarding.

If the fact that marijuana activates the same receptor system as opiates (like heroin, morphine, oxycontin, etc.) surprises you, you should read on.

The opioid system in turn activates the dopamine reward pathway I’ve discussed in numerous other posts (look here for a start). This is the mechanisms that is assumed to underlie the rewarding, and many of the addictive, properties of essentially all drugs of abuse.

But we’re not done!

Without the activation of the CB1 receptors, it seems that opiates, alcohol, nicotine, and perhaps stimulants (like methamphetamine) lose their rewarding properties. This would mean that drug reward depends much more heavily on the cannabinoid receptor system than had been previously thought. Since this is the main target for THC, it stands to reason that the same would go for marijuana.

So what?! Why is marijuana addictive?

Since there’s a close connection between the targets of THC and the addictive properties of many other drugs, it seems to me that arguing against an addictive potential for marijuana is silly.

Of course, some will read this as my saying that marijuana is always addictive and very dangerous. They would be wrong. My point is that marijuana can not be considered as having no potential for addiction.

As I’ve pointed out many times before, the proportion of drug users that become addicted, or dependent, on drugs is relatively small (10%-15%). This is true for almost all drugs – What I’m saying is that it is likely also true for marijuana (here is a discussion of physical versus psychological addiction and their bogus distinction).

Citation:

Ghozland, Matthes, Simonin, Filliol, L. Kieffer, and Maldonado (2002). Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors. Journal of Neuroscience, 22, 1146-1154.

The benefits of marijuana: Things are far from all bad for weed

Marijuana can certainly be beneficial.

It’s true that essentially every drug has some abuse liability. However, somewhere in the vicinity of 85% of those who try any given drug will never develop abuse or addiction problems (yes there are probably variations based on specific drugs, but that’s a good estimate).  As we all know, marijuana is a drug that receives a lot of attention and drives intense debate when it comes to its benefits and harms.  While most of the posts on my site focus on the other 15%, there is, and continues to be, evidence for the benefits of marijuana and other drugs that directly activate cannabinoid receptors.

Some of the shown benefits of marijuana

THC, the active ingredient in cannabis, is known to cause sedation, euphoria, decrease in pain sensitivity, as well as memory and attention impairments.  But there are some aspects of the cannabinoid receptors that have been shown to be effective in AIDS, glaucoma and cancer treatments.

Stimulation of cannabinoid receptors causes an increase in appetite and therefore helps with the wasting syndrome often seen as a side effect in AIDS treatments or those with eating disorders. Since THC activation decreases intra-ocular pressure, another area in which marijuana has been proven to be effective is in the treatment of glaucoma.  THC’s anti-emetic (or anti-vomiting) properties also make it a very useful tool for combating the side effects of cancer treatments.

Still, the activation of cannabinoid receptors is not synonymous with smoking weed. In fact, there are a number of other possible ways to consume THC and other cannabinoid-receptor activators. Also, THC is a potent immune suppressing agent, so in someone who already has a compromised immune system, such as AIDS patients, marijuana and other THC compounds could increase the risk of infection.

Future promise for the use of THC in medicine

There is some evidence that of the 2 major THC receptors (CB1 and CB2), one is associated with the immuno-suppression that occurs after chronic usage and the other is associated with the the more beneficial aspects we’d discussed. In the future, we may be able to produce a compound that activate only the behavioral effects and could therefore be used more safely for AIDS patients. Marijuana lovers will say that we should leave things as they are, but I’m all for less immuno-suppression with my cancer therapy.

Again, just because activation of THC receptors can provide the above benefits does not necessarily mean one should smoke marijuana. As usual, the benefits and risks have to be considered and one has to reach an educated, informed, conclusion. Still, there’s little doubt that in some situations, the use of marijuana, or other THC activators is not only prudent, but indeed recommended.

Co-authored by: Jamie Felzer

Marijuana addiction – Literature search results on marijuana facts

My recent post on marijuana’s addictive potential received some scathing comments from readers who seem to think that the scientists have already agreed that marijuana addiction (called marijuana dependence in the field) does not exist. So, I’ve compiled this little list of research articles. I’ve made certain to only use articles that have been cited often (in other work), meaning that their content has made an impact. Each of these papers has been cited at least 50 times (except for the very recent last review with about 40). Once again, I find it odd that only marijuana users are so insistent about their drug having no negative aspects whatsoever.

1. Laura Jean Bierut, MD; Stephen H. Dinwiddie, MD; Henri Begleiter, MD; Raymond R. Crowe, MD; Victor Hesselbrock, PhD; John I. Nurnberger, Jr, MD, PhD; Bernice Porjesz, PhD; Marc A. Schuckit, MD; Theodore Reich, MD (1998). Familial Transmission of Substance Dependence: Alcohol, Marijuana, Cocaine, and Habitual Smoking. Archives of General Psychiatry, 55, pp. 982-988.

2. Budney A. J.; Novy P. L.; Hughes J. R (1999). Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction, 94, pp. 1311-1322.

3. AJ Budney, ST Higgins, KJ Radonovich, PL Novy (2000). Adding voucher-based incentives to coping skills and motivational enhancement improves outcomes during treatment for marijuana dependence. Journal of Consulting and Clinical Psychology, 68, 1051-1061.

4. William R. True, Andrew C. Heath, Jeffrey F. Scherrer, Hong Xian, Nong Lin, Seth A. Eisen, Michael J. Lyons, Jack Goldberg, Ming T. Tsuang (1999). Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 8, 391-397.

5. Aimee L. McRae, Pharm.D., Alan J. Budney, Ph.D., Kathleen T. Brady, M.D., Ph.D. (2003). Treatment of marijuana dependence: a review of the literature. Journal of Substance Abuse Treatment, 24, 369-376.