Reclassification recommendations for drug in 'magic mushrooms'

Reclassification recommendations for drug in 'magic mushrooms'

If phase III clinical trials are successful, researchers suggest categorizing the drug as schedule IV

September 26, 2018

Science Daily/Johns Hopkins Medicine

In an evaluation of the safety and abuse research on the drug in hallucinogenic mushrooms, Johns Hopkins researchers suggest that if it clears phase III clinical trials, psilocybin should be re-categorized from a schedule I drug -- one with no known medical potential -- to a schedule IV drug such as prescription sleep aids, but with tighter control.

 The researchers summarize their analysis in the October print issue of Neuropharmacology.

 "We want to initiate the conversation now as to how to classify psilocybin to facilitate its path to the clinic and minimize logistical hurdles in the future," says Matthew W. Johnson, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "We expect these final clearance trials to take place in the next five years or so."

Following the Controlled Substances Act of 1970, any drug with the potential for abuse is categorized based on criteria that take into account whether the drug has accepted medical use, and its safety and the potential for abuse. Although preliminary research studies suggest that psilocybin may be effective for smoking cessation and for disorders such as cancer-specific depression and anxiety, it must clear phase III clinical trials before the Food and Drug Administration can be petitioned to reclassify it.

Studies in animals and humans both show low potential for abuse, the researchers say. When rats push a lever to receive psilocybin, they don't keep pushing the lever like they do for drugs such as cocaine, alcohol or heroin. When it comes to human studies, people who have used psilocybin typically report using it a few times across their lifetime.

As for safety, studies show it frequently falls at the end of the scales with the least harm to users and society, say the researchers. Psilocybin also is lowest in the potential for lethal overdose as there is no known overdose level.

"We should be clear that psilocybin is not without risks of harm, which are greater in recreational than medical settings, but relatively speaking, looking at other drugs both legal and illegal, it comes off as being the least harmful in different surveys and across different countries," says Johnson.

That being said, although psilocybin is relatively less harmful than other drugs and not prone to compulsive abuse, the researchers don't recommend releasing psilocybin into patients' hands even with a prescription. "We believe that the conditions should be tightly controlled and that when taken for a clinical reason, it should be administered in a health care setting monitored by a person trained for that situation," says Johnson. The researchers foresee that the process for psilocybin use in the clinic would be similar to how an anesthesiologist prescribes and administers a drug, minimizing the potential for abuse or harm.

https://www.sciencedaily.com/releases/2018/09/180926082159.htm

'Magic mushrooms' may 'reset' the brains of depressed patients

October 13, 2017

Science Daily/Imperial College London

Patients taking psilocybin to treat depression show reduced symptoms weeks after treatment following a 'reset' of their brain activity.

The findings come from a study in which researchers from Imperial College London used psilocybin -- the psychoactive compound that occurs naturally in magic mushrooms -- to treat a small number of patients with depression in whom conventional treatment had failed.

In a paper, published today in the journal Scientific Reports, the researchers describe patient-reported benefits lasting up to five weeks after treatment, and believe the psychedelic compound may effectively reset the activity of key brain circuits known to play a role in depression.

Comparison of images of patients' brains before and one day after they received the drug treatment revealed changes in brain activity that were associated with marked and lasting reductions in depressive symptoms.

The authors note that while the initial results of the experimental therapy are exciting, they are limited by the small sample size as well as the absence of a control group -- such as a placebo group -- to directly contrast with the patients.

Dr Robin Carhart-Harris, Head of Psychedelic Research at Imperial, who led the study, said: "We have shown for the first time clear changes in brain activity in depressed people treated with psilocybin after failing to respond to conventional treatments.

"Several of our patients described feeling 'reset' after the treatment and often used computer analogies. For example, one said he felt like his brain had been 'defragged' like a computer hard drive, and another said he felt 'rebooted'. Psilocybin may be giving these individuals the temporary 'kick start' they need to break out of their depressive states and these imaging results do tentatively support a 'reset' analogy. Similar brain effects to these have been seen with electroconvulsive therapy."

Over the last decade or so, a number of clinical trials have been conducted into the safety and effectiveness of psychedelics in patients with conditions such as depression and addictions, yielding promising results.

In the recent Imperial trial, the first with psilocybin in depression, 20 patients with treatment-resistant form of the disorder were given two doses of psilocybin (10 mg and 25 mg), with the second dose a week after the first.

Nineteen of these underwent initial brain imaging and then a second scan one day after the high dose treatment. Carhart-Harris and team used two main brain imaging methods to measure changes in blood flow and the crosstalk between brain regions, with patients reporting their depressive symptoms through completing clinical questionnaires.

Immediately following treatment with psilocybin, patients reported a decrease in depressive symptoms -- corresponding with anecdotal reports of an 'after-glow' effect characterised by improvements in mood and stress relief.

Functional MRI imaging revealed reduced blood flow in areas of the brain, including the amygdala, a small, almond-shaped region of the brain known to be involved in processing emotional responses, stress and fear. They also found increased stability in another brain network, previously linked to psilocybin's immediate effects as well as to depression itself.

These findings provide a new window into what happens in the brains of people after they have 'come down' from a psychedelic, where an initial disintegration of brain networks during the drug 'trip', is followed by a re-integration afterwards.

Dr Carhart-Harris explained: "Through collecting these imaging data we have been able to provide a window into the after effects of psilocybin treatment in the brains of patients with chronic depression. Based on what we know from various brain imaging studies with psychedelics, as well as taking heed of what people say about their experiences, it may be that psychedelics do indeed 'reset' the brain networks associated with depression, effectively enabling them to be lifted from the depressed state.

The authors warn that while the initial findings are encouraging, the research is at an early stage and that patients with depression should not attempt to self-medicate, as the team provided a special therapeutic context for the drug experience and things may go awry if the extensive psychological component of the treatment is neglected. They add that future studies will include more robust designs and currently plan to test psilocybin against a leading antidepressant in a trial set to start early next year.

Professor David Nutt, Edmond J. Safra Professor of Neuropsychopharmacology and director of the Neuropsychopharmacology Unit in the Division of Brain Sciences, and senior author of the paper, added: "Larger studies are needed to see if this positive effect can be reproduced in more patients. But these initial findings are exciting and provide another treatment avenue to explore."

https://www.sciencedaily.com/releases/2017/10/171013091018.htm

Magic mushroom compound psilocybin could provide new avenue for antidepressant research

May 17, 2016

Science Daily/The Lancet

Psilocybin -- a hallucinogenic compound derived from magic mushrooms -- may offer a possible new avenue for antidepressant research, according to a new study published in The Lancet Psychiatry today.

The small feasibility trial, which involved 12 people with treatment-resistant depression, found that psilocybin was safe and well-tolerated and that, when given alongside supportive therapy, helped reduce symptoms of depression in about half of the participants at 3 months post-treatment. The authors warn that strong conclusions cannot be made about the therapeutic benefits of psilocybin but the findings show that more research in this field is now needed.

"This is the first time that psilocybin has been investigated as a potential treatment for major depression," says lead author Dr Robin Carhart-Harris, Imperial College London, London, UK. "Treatment-resistant depression is common, disabling and extremely difficult to treat. New treatments are urgently needed, and our study shows that psilocybin is a promising area of future research. The results are encouraging and we now need larger trials to understand whether the effects we saw in this study translate into long-term benefits, and to study how psilocybin compares to other current treatments."

Depression is a major public health burden, affecting millions of people worldwide and costing the US alone over $200 billion per year. The most common treatments for depression are cognitive behaviour therapy (CBT) and antidepressants. However, 1 in 5 patients with depression do not respond to any intervention, and many relapse.

"Previous animal and human brain imaging studies have suggested that psilocybin may have effects similar to other antidepressant treatments," says Professor David Nutt, senior author from Imperial College London "Psilocybin targets the serotonin receptors in the brain, just as most antidepressants do, but it has a very different chemical structure to currently available antidepressants and acts faster than traditional antidepressants."

The trial involved 12 patients (6 women, 6 men) with moderate to severe depression (average length of illness was 17.8 years). The patients were classified as having treatment-resistant depression, having previously had two unsuccessful courses of antidepressants (lasting at least 6 weeks). Most (11) had also received some form of psychotherapy. Patients were not included if they had a current or previous psychotic disorder, an immediate family member with a psychotic disorder, history of suicide or mania or current drug or alcohol dependence.

Patients attended two treatment days -- a low (test) dose of psilocybin 10mg oral capsules, and a higher (therapeutic) dose of 25mg a week later. Patients took the capsules while lying down on a ward bed, in a special room with low lighting and music, and two psychiatrists sat either side of the bed. The psychiatrists were present to provide support and check in on patients throughout the process by asking how they were feeling. Patients had an MRI scan the day after the therapeutic dose. They were followed up one day after the first dose, and then at 1, 2, 3, and 5 weeks and 3 months after the second dose.

The psychedelic effects of psilocybin were detectable 30 to 60 minutes after taking the capsules. The psychedelic effect peaked at 2-3 hours, and patients were discharged 6 hours later. No serious side effects were reported, and expected side effects included transient anxiety before or as the psilocybin effects began (all patients), some experienced confusion (9), transient nausea (4) and transient headache (4). Two patients reported mild and transient paranoia.

At 1 week post-treatment, all patients showed some improvement in their symptoms of depression. 8 of the 12 patients (67%) achieved temporary remission. By 3 months, 7 patients (58%) continued to show an improvement in symptoms and 5 of these were still in remission. Five patients showed some degree of relapse.

The patients knew they were receiving psilocybin (an 'open-label' trial) and the effect of psilocybin was not compared with a placebo. The authors also stress that most of the study participants were self-referred meaning they actively sought treatment, and may have expected some effect (5 had previously tried psilocybin before). All patients had agreement from their GP to take part in the trial. They add that patients were carefully screened and given psychological support before, during and after the intervention, and that the study took place in a positive environment. Further research is now needed to tease out the relative influence of these factors on symptoms of depression, and look at how psilocybin compares to placebo and other current treatments.

Writing in a linked Comment, Professor Philip Cowen, MRC Clinical Scientist, University of Oxford, Oxford, UK, says: "The key observation that might eventually justify the use of a drug like psilocybin in treatment-resistant depression is demonstration of sustained benefit in patients who previously have experienced years of symptoms despite conventional treatments, which makes longer-term outcomes particularly important. The data at 3 month follow-up (a comparatively short time in patients with extensive illness duration) are promising but not completely compelling, with about half the group showing significant depressive symptoms. Further follow-ups using detailed qualitative interviews with patients and family could be very helpful in enriching the assessment."

https://www.sciencedaily.com/releases/2016/05/160517083044.htm