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Pr. Frances Levine: Treating Cannabis Addiction

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Pr Frances Levine: Treating Cannabis Addiction




Hello! You’re on MD-FM INSIGHT, the first medical web radio. Today we’ll be devoting our "Question & Answer" program to the treatment of cannabis addiction…


And for this, we interviewed Dr. Frances Levine, Kennedy Leavy professor of psychiatry at Columbia University, and past president of the American Academy of Addiction Psychiatry. During the annual meeting of the American Psychiatric Association’s annual meeting, in New York last May, Dr. Levine gave a presentation on the most recent updates concerning research in potential treatments for cannabis addiction and cannabis withdrawal…



Hello Dr. Levine, first of all, can you tell us why cannabis-addiction hasn’t really been studied for very long?



One of the issues is that with cannabis, people did not understand that there was a cannabis withdrawal syndrome, even though there was data, even from the 1970s, suggesting the case –there were a lot of laboratory studies that were done demonstrating that. But, clinically, people weren’t really aware of it and, when they stopped using marijuana, they attributed it often to something else –often people are also smoking cigarettes or, their irritability –they were attributing it to their psychiatric disorder that they may have at the same time, and they were not recognizing that there was a clear withdrawal syndrome associated with cannabis, similar to what was true about cocaine 25 years ago, in the early 80, the American Psychiatric Association had a textbook, in which they didn’t even recognize cocaine withdrawal existed. So it isn’t surprising that something that isn’t dramatic, such as what you see with opiate withdrawal, that it might be under-recognized.



OK and now that’s it’s officially recognized, in the DSM-5, are there any compound under investigation that looks promising to treat cannabis withdrawal or addiction?



There’s been a number of studies done for cannabis use disorders that have looked at psychotherapy, there are very little that have been done for pharmacologic treatments. When I say “what’s promising” to you, what I have to emphasize is that we are usually talking about maybe one study –one double blind randomized control trial, often these trials are small, often there’s high drop out rates, so you have to take it with a grain of salt, as I tell you what has been promising.



OK… and can you give us examples?



Yes, gabapentine has been looked at and found to be helpful in reducing cannabis use and actually increase abstinence, also helps with executive functioning, compared to placebo. Dronabinol has promise in terms of reducing withdrawal symptoms and improving retention, but hasn’t been shown to be superior to placebo in terms of abstinence rates or even reduction in use. And some of that may be due to the bioavailability of dronabinol. And now what we are interested in looking at is nabilone because it has higher bioavailability and can be given once a day and has been shown to be particularly promising in the laboratory. Also buspirone has been looked at –there’s some data saying that it might be helpful but, again, all of these studies have the problem of being small, and high drop out rates. So we really need a lot more work.



Ok so a lot of molecules, and is there one that looks more promising than the others?  



What’s I think really the most promising at the moment, but it really needs to be replicated, is N-acetyl-Cysteine, which is a glutamate modulator, and has been thought that it might have some utility for cannabis use disorders in adolescent populations. These adolescents also got contingency management, which is a strategy where you pay them or give them vouchers for progressively … they get progressively more value vouchers as their urines continue to be positive. With that behavioral platform and n-acetyl-cysteine, that worked better than placebo. It definitely needs to be replicated, the United States clinical trials network, they are going to try replicate that finding in adults -- what we won’t know is whether or not you need the platform of contingency management to make the medication be effective but, nonetheless, to me, that’s one of the more promising options to look at, at the moment.



And how long are these patients treated for in these trials?



Generally most of these studies are, at best, 12 weeks long, so you are talking about very short-term evaluations. And, clearly, we don’t know how well patients would do if they were maintained on it for a longer period of time… nor do we know, if we take people off at 12 weeks, whether you still see an advantage at 6 months or 1 year, we don’t have the data yet for that. I mean, we know about opiates treatments, and generally, it’s unless you maintain people for a long period of time on medication, they tend to relapse pretty quickly if you take them off after a short period of time.



And I was wondering could unrecognized ADHD be a factor for cannabis use?



It’s interesting… I mentioned this morning that there was this large cannabis trial in adolescents and a substantial minority of them –I’d have to go back and look at the paper but it was something between 30 and 40 percent of these kids – had ADHD and they were allowed to be treated but there was no data presented regarding what was the nature of the treatment, how long they were treated and you would have to believe as a clinician that, if they were well treated for their ADHD that would facilitate the benefit of the other psychotherapies that are being applied.



OK… so there hasn’t been any study looking at a treatment for ADHD and cannabis dependence? 



I think there’s been one paper that I’ve seen that has looked at pure cannabis dependent patients who were adults and who had ADHD and the medication they looked at was atomoxetine but, again, it was very small study, there was a high drop out and frankly it didn’t look that useful, you know, there was only maybe a slight signal… I’m not convinced that atomoxetine is the way to go, although it makes some sense if you like to use that because of lower abuse liability, but I do think that there needs to be work looking at methylphenidate. What I will say is that there has been a number of adolescents studies–one is by Paula Riggs, that was a large trial in the clinical trials network and it was adolescents with ADHD who were given OROS methylphenidate and many of these kids were dependent on marijuana and in that study, actually the primary outcome measure was negative for ADHD but the secondary outcomes were positive.



What were the first and secondary outcomes?



So the primary outcome was asking the adolescents if they felt better in terms of their ADHD and the study was negative. When they asked the parents, there was a significant difference so I think in that study, if they had used the parents outcome of evaluating their child, it would have been a significant study. But it didn’t change their drug use in that study… but again one of the things that we also heard this morning is that maybe and adolescents and adults need to be on higher doses that are above FDA approved but again it needs to be researched at this point.



So higher methylphenidate doses?



It’s all supposition at this point but there’s work by a woman in Sweden –Martha Kastenias –who did work with amphetamine abusers, she went up to 180 mg or OROS methylphenidate, which is twice the FDA approved dose, and found that in that case, in that population, these were people with ADHD –their ADHD improved as well as their amphetamine use, so at least in stimulant abusers, higher doses might be needed. In terms of cannabis dependent patients –I don’t know.



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