The good, the bad, and the intoxicated: Neuroadaptations underlying effects of cannabis and psilocybin (ab)use

Humans have been looking for ways to alter their consciousness by taking drugs that are found in nature since time immemorial. Today, substances like cannabis and psychedelics are used by many people, for a myriad of recreational and therapeutic reasons. Importantly, as both recreational and therapeutic interest into these substances grows, so will use. Thus a pertinent question is how these substances work to elicit such effects, and what the long-term consequences of use are. The latter is of particular importance, as single doses of these substances have been suggested to produce neuroadaptations that underlie acute and long-term behavioral changes. Such behavioral consequences can be seen as maladaptive, like increased tolerance to the rewarding effects of the drug, resulting in the user needing to increase the dose and frequency of use; or adaptive, with users experiencing sustained increases in well-being, long after acute drug effects have worn off. As the underlying neuroadaptations giving rise to such effects have not been systematically assessed in humans, several experimental studies were conducted in order to gain more insight into markers that reflect acute neuroadaptations induced by single and repeated drug exposure, which may underlie previously established behavioral effects of cannabis and psilocybin.