One of the early concerns that dominated the medical cannabis discussion was over both the addictive potential and long-term effects of cannabis. For decades, it has generally been understood by the medical community that cannabis is not physically addictive but can be psychologically addictive. To differentiate, individuals addicted to alcohol cannot suddenly end consumption without risk of death or serious health consequences, because their bodies have learned to literally need alcohol. In contrast, even a frequent cannabis consumer can end consumption immediately without serious health risk. However, this transition might be severely uncomfortable due to the psychological dependence of cannabis use. Some anti-cannabis advocates and researchers alike have pushed for the notion that this dependence is life-long. Researchers from Geneva, Switzerland recently pressed one step forward to directly answer this question by observing changes in brain chemistry during and after chronic cannabis use.
To back up, what is addiction and what causes addiction? As researchers note, “the addictive effects of virtually all drugs…are thought to be mediated through activation of mesolimbic dopamine projections to the nucleus accumbens.” Essentially, a neurotransmitter, dopamine, is activated to a greater degree than normal, causing an increased interaction with the part of the brain that deals with decision making, risk, and reward. Dopamine is responsible for a multitude of signaling tasks, but perhaps the most known and most important job is signaling reward. When a user consumes a drug, dopamine is released in the brain, essentially rewarding the user for consuming the drug and teaching him/her to take it again (thus addiction). Unfortunately, the brain then learns to compensate and expect that reward, which is why the density of dopamine receptors decreases as a result of consistent drug use and in some cases, does not recover. Researchers therefore decided to establish the effect of chronic THC exposure on dopamine receptor levels, as well as the reaction to activating those receptors via quinpirole, a dopamine receptor agonist.
To do this, researchers employed lab mice, which have similar brain structures to humans. Control rats meant for baseline comparison received injections of saline (salt water) daily while the rest received a solution of THC adjusted to reflect body weight (1 mg/kg/day) for either one, two, or three weeks with measurements taken exactly 24 hours after the final dose in each case. Additionally, and perhaps most importantly, the three week group continued to have measurements taken at one, two, and six weeks after the end of the treatment, to help establish the long-term effects of THC use. Obviously, counting the actual number of dopamine receptors in rodent brains was impossible due to the number and small size, so to get around this issue, researchers prepared a radioactive tracer that bonds to and illuminates the position of dopamine receptors in brain tissue. With this type of radioactive tracing, slices of brain tissue could then be exposed to photographic film to make a close measurement of the actual number, density, and position of dopamine receptors.
To measure the effect of activating those receptors, which was important to establish any behavioral differences in chronic THC users vs. baseline response, researchers injected rodents with either saline or quinpirole both before the THC program and on the final day. Since quinpirole activates dopamine receptors, the idea here was that researchers could then perform a motor/locomotion test to determine if THC rodents were affected more or less strongly by dopamine receptor activation. After quinpirole injection, rodents were therefore placed in an open field container, and researchers measured the distance the rodents traveled horizontally, as well as the number of vertical rearings (standing on their hind legs) as a measurement of locomotion. Finally, researchers measured the amount of time rodents spent in the center of the open-field, which is related to locomotor activity but also “some aspect of emotionality, including anxiety.”
As it turned out, THC treatment had a significant effect. In fact, even after one week of daily treatment, dopamine receptor density had risen in the ventral tegmental area (VTA) and in its striatal terminal fields (the caudate putamen and most importantly the nucleus accumbens involved in reward decision making mentioned earlier). The rate of increase was shown to be specific to the area of the brain being examined, meaning that dopamine receptor increases occur in specific areas, as opposed to a general area. However, perhaps most relevant to our readers, all of these effects had disappeared by six weeks after treatment (and in some brain areas, only three!), indicating that these changes are not only reversible, but also that the brain readjusts quickly.
Secondly, daily THC dosing temporarily increased the functional activity of both pre and post-synaptic dopamine receptors. Although at one week of daily THC treatment no significant changes were observed, by three weeks, injection of quinpirole had a greater effect than normal, with activation of dopamine receptors causing rodents on the THC program to move less than rodents on saline. This indicates that the response to dopamine receptors was temporarily heightened as a result of consuming THC. However, again, these differences disappeared entirely within six weeks of ending THC treatment.
In other words, while there is certainly an interaction between dopamine receptors and extended cannabis use we have no reason to believe that these changes are permanent or negative. To the contrary, these changes appear to be entirely reversible. One caveat to the experiment, as researchers note, is perhaps on an even greater time-scale, for instance years of daily cannabis use, we would observe effects that are unseen here. Indeed, anti-cannabis proponents tend to seize on this unknown as a reason for rejecting medical cannabis treatment. Of course, the same argument could be applied to extended caffeine use and a multitude of other pharmaceuticals on the market that have not been evaluated long-term. At the time being, especially for individuals who experience a boost in quality of life from the use of daily cannabis, we have no grounds to believe that cannabis is physically addictive or harmful and look forward to continuing to follow groundbreaking research in the field of cannabis science.
Benjamin Tournier, Stergios Tsartsalis, Andrea Dimiziani, et al. Time Dependent Effects of Repeated THC Treatment on Dopamine D2/3R-mediated signaling in the midbrain and striatum. Behavioral Brain Research (2016). DOI: 10.1016/j.bbr.2016.05.045