How psychedelic drugs achieve their potent health benefits

A controversial topic! If we only could turn off or reduce the addictive or dependence properties!

"Psychedelic drugs are promising treatments for many mental-health conditions, but researchers don’t fully understand why they have such powerful therapeutic effects. Now, a study in mice suggests that psychedelics all work in the same way: they reset the brain to a youthful state in which it can easily absorb new information and form crucial connections between neurons. ...
The findings raise the prospect that psychedelic drugs could allow long-term changes in many types of behavioural, learning and sensory system that are disrupted in mental-health conditions. ..."

"... a new study in mice shows that psychedelic drugs are linked by their common ability to reopen such critical periods, but differ in the length of time the critical period is open—from two days to four weeks with a single dose. ...
In 2019, her team found that MDMA [ecstasy], a psychedelic drug that arouses feelings of love and sociability, opens a critical period in mice. ...
to find in the current study that other psychedelic drugs without prosocial properties could also reopen critical periods. ...
For the current study, Dölen's team looked at the reopening potential of five psychedelic drugs—ibogaine, ketamine, LSD, MDMA and psilocybin ...
For mice given ketamine, the critical period of social reward learning stayed open in the mice for 48 hours. With psilocybin, the open state lasted two weeks. For mice given MDMA, LSD and ibogaine, the critical period remained open for two, three and four weeks, respectively. ...

Next, the scientists looked at psychedelic drugs' impact on molecular mechanisms. First, in mouse brain cells, they examined a binding point, known as a receptor, for the neurotransmitter serotonin. The researchers found that while LSD and psilocybin use the serotonin receptor to open the critical period, MDMA, ibogaine and ketamine do not.

To explore other molecular mechanisms, the research team turned to ribonucleic acid (RNA), a cousin to DNA that represents which genes are being expressed (producing proteins) in the mice's cells. The researchers found expression differences among 65 protein-producing genes during and after the critical period was opened.

About 20% of these genes regulate proteins involved in maintaining or repairing the extracellular matrix ..."

From the abstract:

"Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness. These drugs have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies. Nevertheless, a unifying mechanism that can account for these shared phenomenological and therapeutic properties remains unknown. Here we demonstrate in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelic drugs. Notably, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Finally, identification of differentially expressed genes in the ‘open state’ versus the ‘closed state’ provides evidence that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening. Together these results have important implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease."

How psychedelic drugs achieve their potent health benefits Mouse studies suggest that drugs from LSD to ecstasy renew the brain’s flexibility — but some scientists are sceptical.

Study Shows Psychedelic Drugs Reopen 'Critical Periods' For Social Learning Johns Hopkins scientists say the findings in mice offer a new explanation for how psychedelic drugs work

Psychedelics reopen the social reward learning critical period (open access)

Gül Dölen, the lead author of this study

Fig. 1: Psychedelics reopen the social reward learning critical period.

Fig. 4: Psychedelics induce metaplasticity.