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Psychedelics Research Expands Treatment Focus

Researchers looking more closely at similarities of compounds and responses.
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Researchers have generally guided their work with classic psychedelics to understanding their effect on specific mental health and wellness issues. For example, looking to MDMA to treat post-traumatic stress disorder (PTSD), psilocybin for major depression, and LSD for cluster headaches.

But the latest trend is looking to expand on that idea and learn more about what these compounds really do.

Researchers are beginning to make headway about how psychedelics work for mental health ailments other than those for which they were originally studied, blurring the distinctions about which psychedelic might be best for which mental health condition.

For example, there are clinical trials with psilocybin to find treatments for methamphetamine and alcohol addiction, opioid dependence, Parkinson’s disease, anorexia, Lyme disease, and even caregiver burnout.

MDMA is being investigated to treat eating disorders, drug addiction, opioid  dependence, autism, and even hangovers. Researchers are working with LSD to treat major depression and anxiety disorders.

An article in the March issue of Science Advances, American Association for the Advancement of Science’s open-access multidisciplinary journal, addressed the challenge facing psychedelics researchers: “The task facing the companies and researchers developing psychedelic compounds is to identify which specific compounds alleviate which specific types of human suffering.”

Researchers are also looking at comparing various psychedelics together in the same clinical trial, such as the trial going on now at University Hospital in Basel, Switzerland comparing LSD, psilocybin, and mescaline.

All three substances are thought to induce prototypical psychedelic effects primarily via stimulation of the 5-HT2A receptor, according to the clinical trial notes. However, there are differences in the substances’ molecular structures and receptor activation profiles which may induce differential subjective effects.

The main objective of the clinical trial is to find out whether LSD, psilocybin, and mescaline produce qualitatively similar subjective alterations of mind and associated brain activity patterns despite their unique receptor activation profiles. The study is investigating psychological (psychometry), physiological, and neuronal (magnetic resonance imaging) variables, with the goal of a better understanding of psychedelic-induced altered states of consciousness in humans.

Another study completed in February compared LSD and psilocybin. “We found no evidence of qualitative differences in altered states of consciousness that were induced by either LSD or psilocybin, except that the duration of action was shorter for psilocybin,” the study concluded.

As with most psychedelics trials, participant size is relatively small, which has a limiting effect on the range of results. For example, Cybin just started its Phase 1/2a first-in-human clinical trial evaluating its CYB003 product for major depressive disorder with just 40 participants.

But there have been larger trials. The Multidisciplinary Association for Psychedelic Studies (MAPS) reports that the second of two Phase 3 trials of MDMA for PTSD will have at least 100 participants, as part of their special protocol agreement with the FDA. Results are expected in October 2023.

And in May, Compass Pathways (Nasdaq: CMPS) presented data from one of the largest randomized, controlled, double-blind studies of psilocybin therapy ever completed, using results from 233 participants.

But finding out more about how psychedelics work inside the human brain is just getting started.

“We’re at the baseline of things being investigated right now,” Dr. Lynn Marie Morski, president of the Psychedelic Medicine Association, said during the 2022 reMind psychedelics forum in Las Vegas, held the day ahead of the MJBiz conference. “But imagine the potential of combining things, trying different types of therapies. We saw psilocybin with cognitive behavioral therapy for smoking cessation. What if we try psilocybin with hypnotherapy? There’s so many different formations and combinations that I hope we do investigate.”

In an interview for the Open Foundation, an organization working to integrate psychedelics into society, Matthew Johnson, professor of psychiatry and behavioral sciences at Johns Hopkins Medicine, said that much of the recent resurgence of interest in psychedelics has been research done with psilocybin.

“Our presumption with many of these research questions is that similar results would be obtained with LSD, mescaline, and the other classic psychedelics,” he said. “But that’s just an assumption. We certainly know that they have a common biological pathway.”

When that psilocybin research is compared to the older research with LSD, there is “substantial commonality,” he said. “But at the same time, we do know that these various psychedelics have shades of different effects, even though the classic psychedelics all have effects at the serotonin 2A receptor. We also know that they differ in their effects at a variety of other receptor sites, and this is likely to account for some of the more subtle differences in subjective effects that people will report.”

He said that sometimes those (effects) might be specific to the individual: Some people will report that psilocybin is more psychologically gentle, while LSD is more abrasive, and other people will report exactly the opposite.

“All of this is reporting from anecdotal or recreational use. It’s going to be really exciting to follow up this initial research with psilocybin and with a wide variety of compounds,” Johnson said. “It could be that they are all very general, but – I’m just speculating here – perhaps one of these other substituted tryptamines might be as effective for cancer-related anxiety as psilocybin, but perhaps comes with less of a chance of difficult acute experiences, or perhaps it’s a shorter or longer duration, in a way that makes it more ideal for treatment.

“I think there’s a lot of potential, and we’re in our infancy in examining these things, so there’s a lot of exciting things to come ahead.”

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