Medical cannabis opponents often point to the addictive potential of cannabis as a reason to oppose its use. Many cannabis users consider it to be non-addictive, but cannabis use disorder (CUD, formerly cannabis dependence) is a clinically defined condition. In 2010, an estimated 13 million cases of CUD were reported worldwide. Over 1.7 million of those cases came from high income regions of North America, representing the highest regional prevalence worldwide. Symptoms include consistent use when it is harmful, either physically, mentally, or socially; strong cravings or desire for cannabis; a failure to reduce or quit use; and inability to control intake. Upon quitting, some individuals experience withdrawal symptoms, as well. There is currently no treatment for CUD or symptoms of withdrawal.
Another major concern regarding the widespread adoption of cannabis as medicine is the risk of long-term psychological effects that stem from its use. Chronic cannabis use has been linked to learning and memory deficits, primarily due to the effect of THC. CBD has long been known to blunt the euphoric effects of THC. Therefore, certain cannabis-based medications, such as Sativex, contain equivalent amounts of THC and CBD. This is partly to market them as being “safer” than THC alone. However, it is unknown if CBD can actually offer any protection against long-term THC use, or CUD.
A recent paper published in the British Journal of Pharmacology has taken on both of these questions. In this work, the authors tested whether or not CBD alone causes CUD and/or cognitive impairments. They then extend these experiments to see if CBD is able to protect against these conditions in mice treated with THC. The results suggest that CBD may not be as protective as it is often presented.
The effects of THC and CBD, separately and in combination, were tested using a couple of different methods. In the first task, mice were trained to listen to audio cues and then stick their nose through one of two holes in the cage. The length of the tone told the mice which hole to choose. Once they were able to consistently perform this task, they were treated with cannabinoids and tested again, only this time the audio cues were reversed. The real test, then, was to see how well they adjusted to the new task. Interestingly, cannabinoid treatment, in any combination, had no effect on their ability to learn the new task.
They also tested memory in these mice. To do this, mice were trained to run through a maze, where they would receive a treat at the end. After sufficient training, they were treated with cannabinoids and placed in the maze. The researchers measured how long it took for the mice to reach the end. This time, the THC had a dose-dependent effect on maze performance. This means that the more THC they were given, the longer it took to get to the end. This is not simply an effect of the mice becoming lazy; by tracking their movements, the researchers showed that they traveled the same distance as untreated mice, suggesting that they had forgotten the correct path. Simultaneous treatment with CBD did not alter this effect. However, CBD treatment alone led to faster maze completion. The authors suggest this may be due to the anti-anxiety effects of CBD.
Finally, the researchers attempted to induce withdrawal symptoms following chronic treatment with either THC, CBD, or both. To do this, they gave mice cannabinoid injections every twelve hours for 4.5 days. Then, they gave the mice an injection of a powerful CB1 receptor blocker. This mimics the abrupt quitting of cannabinoid use. Following this final treatment, the mice were observed for signs of withdrawal, including head shakes, head scratching, and paw tremors. The results for both cannabinoids were mixed. For example, rapidly halting THC use led to a moderate increase in head scratching, but a major increase in paw tremors. However, halting CBD use led to a major increase in head scratching, but virtually no paw tremors. The results for halting CBD+THC together were similarly mixed. This demonstrates that CBD does not necessarily halt the development of CUD in mice.
CBD is often considered a bulwark against the negative cognitive effects of THC. This research demonstrates that, for some of these effects, this may not be the case. However, there are some shortcomings that somewhat undercut these findings. For example, the type of mice they used for this study are known to be less effected by THC than other laboratory strains. Therefore, the finding that THC did not affect their ability to learn a new task is suspect. Further, it is chronic cannabis use that results in these cognitive effects, but they were testing the effects of a single cannabinoid dose. It may be that their experimental design does not allow them to detect protection against long term damage.
The link between CBD and cannabis use disorder is interesting, but similarly muddy. CUD is hard to study in mice, because cannabinoids have a tendency to stick around in the body. Therefore, halting cannabis treatment leads to a slow decline of cannabinoids in the system. This is the reason for using CB1 blockers. However, CUD in humans takes the same gradual path, so it’s hard to know if these experiments accurately reflect reality. Further, while the authors tested CB1 blockers, and a number of others known to interact with CBD, they did not use CB2 blockers. Most likely, there are no CB2-specific blockers, so the experiment can’t be done. But in order to truly determine whether or not CBD use leads to CUD, it will be necessary to block both CB receptors.
Regardless, these experiments introduce doubt concerning the protective role of CBD. If cannabis, and specifically THC, is going to be used as a long-term treatment, it is critical that we have a clear understanding of the risks presented, and the limitations of our ability to minimize those risks.