This is the original version of an article that was written by Matt Field and edited for The Conversation, you can find that version here.
More than 1.2 million Americans per year seek treatment for problems with their marijuana (or cannabis) use. Cannabis use disorder is recognised in the same category as other substance use disorders (‘addictions’), in the Diagnostic and Statistical Manual of Mental Disorders, and up to 1% of the European population may warrant this diagnosis. Psychological treatments such as motivational interviewing and cognitive behaviour therapy may be effective, although there have been very few controlled trials of these therapies. A recent review concluded that there were no effective medications for the prevention of relapse to cannabis use.
Like other addictive drugs, Delta-9-tetrahydrocannabinol (THC; the main psychoactive ingredient in cannabis), produces its rewarding effects by stimulating dopamine release in the brain’s reward system, a network of brain structures including the Nucleus Accumbens (NAcc) and the ventral tegmental area (VTA). Therefore, one potential way to treat addictions would be to give medications that block dopamine activity in the reward system, such as the dopamine antagonist drugs that are used to treat schizophrenia. Unfortunately, these drugs have some unpleasant side-effects. More fundamentally, dopamine antagonists block all forms of reward, not just drug-induced reward. Therefore, the search is on for drugs that can interfere with drug-induced reward without producing unpleasant side-effects, and without interfering with the response to other rewards.
A study recently published in Nature Neuroscience has identified a promising potential new medication for cannabis use disorders. The drug, RO 61-8048, leads to increases in levels of kynurenic acid (KYNA). Through a fairly complicated mechanism, what this does is block the ability of THC (and similar compounds) to increase dopamine activity in the brain’s reward centre. Most importantly, although the drug can blunt the effect of THC on dopamine levels, it has no effect on dopamine levels when given on its own. In this paper, the authors conducted a series of studies with rodents and primates, and they found that:
- The drug prevented the increase in dopamine levels in NAcc and the VTA that normally occurred after infusion of THC.
- The drug blocked the reinforcing effects of THC: after receiving the drug, animals were less likely to press a lever in order to obtain injections of THC or a related compound.
- The drug could block the rewarding effects of THC. For example, animals will normally press a lever to receive THC if they have just been given an injection of THC or if they have been presented with environmental signals that THC was available (these tests are considered animal models of relapse to drug use). The drug reduced both of these effects.
- These effects of the drug were specific to THC, because the drug did not affect the reinforcing properties of another reward: food. Animals were prepared to press a lever in order to win food pellets, regardless of whether they had received the drug or not.
- At the doses studied, the drug had no effect on working memory, and did not change the memory-impairing effects of THC.
These findings are potentially important because has been very difficult to develop medications that block drug-induced reward without also interfering with the response to other rewards. The safety of the drug, and its effectiveness as a treatment for cannabis use disorders, should now be studied in human volunteers.
We should be cautious, however. Even if the drug is safe in humans, and it can reduce the rewarding effects of cannabis, this will not make it a panacea for cannabis use disorders. Medications for other substance use disorders, such as naltrexone for alcohol use disorders and buprenorphine for opiate use disorders are prescribed because they reduce the rewarding effects of alcohol or heroin if those drugs are consumed. Although the drugs are effective, if a patient decides that they want to experience the rewarding effects of alcohol or heroin again, all they have to do is stop taking their medication. This is also likely to be the case for RO 61-8048 and cannabis use disorders. Medication implants and depot formulations may partly solve this problem.