While modern research increasingly finds that psilocybin, the active psychoactive compound in magic mushrooms, offers promising therapeutic outcomes for many otherwise treatment-resistant conditions, taking the plunge into the psychedelic realm can feel daunting for many people.
Similar to the “reefer madness” propaganda of the past pertaining to cannabis, we’re gradually navigating away from old assumptions that psilocybin and other psychedelic compounds are a recipe for disaster — that a trip is a one-way ticket to psychosis and dangerous mental health implications.
Research has found that emergency room visits over psilocybin use is extremely rare, and most common negative symptoms related to psilocybin use were due to poor mindset, setting, mixing substances and ultimately resolved within 24 hours.
While most medical treatments come with some risks, a new study looked to further investigate the notable adverse effects for psilocybin treatment pertaining to anxiety and depression. Researchers at the University of Georgia, Larkin University and Palm Beach Atlantic University published their review in JAMA Psychiatry, which involved a meta-analysis of double-blind clinical trials involving psilocybin treatment for depression and anxiety between 1966 and 2023.
The study notes a number of expected adverse effects from psilocybin therapy for depression and anxiety, but researchers did not find an association with paranoia and transient thought disorder as these symptoms were reported with comparatively low frequency to others.
Looking Back at Past Research To Inform the Future
“Psilocybin has been studied in the treatment of depression and anxiety disorders,” authors begin. “Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety.”
To evaluate adverse effects of therapeutic psilocybin doses for depression and anxiety treatment, researchers evaluated studies including randomized clinical trials comparing psilocybin with placebo groups or another comparator. They also grouped doses into low (1-3 mg), moderate (10-20 mg) and high (20-30 mg) categories based on previous clinical data.
The analysis included six studies with a total of 528 participants.
In general, participants experienced adverse effects immediately or within 24 hours of psilocybin administration. Contrary to some of the negative stereotypes surrounding psilocybin and other psychedelics, study authors noted that psilocybin was “not associated with the risk of paranoia and transient thought disorder,” which is characterized by the sudden onset of psychotic symptoms.
Two adverse effects occurred in all six studies — headache (an incidence ranging from 2% to 66%) and nausea (4% to 48%) — while anxiety was documented in three studies (4% to 26% incidence rate). Authors noted that all adverse effects had an estimated value of less than 50% except elevated blood pressure.
Psilocybin Produces ‘Tolerable Acute Adverse Effects,’ Quick Resolution
“A summary of the acute adverse effects of psilocybin in treating depression and anxiety is needed for healthcare professionals to identify expected adverse effects and provide effective patient counseling,” researchers note in their discussion. “… The results overall suggest a statistically significant incidence of headache, nausea, anxiety, dizziness, and elevated blood pressure… Given the psilocybin mechanism of action, these adverse effects are expected as they are similar among serotonergic antidepressants.”
The study notes that there were three cases of paranoia with high-dose psilocybin across 128 patients, with five patients in two studies experiencing transient thought disorder. Researchers noted that all studies used a therapist or facilitator to assist patients — which could have potentially prevented increased severity of complications.
Researchers add that incidence of paranoia and transient thought disorder appears to be low, but they are still adverse effects worth exploring in the future.
“In this systematic review and meta-analysis, therapeutic doses of psilocybin appeared to produce tolerable acute adverse effects that typically resolved within 24 to 48 hours,” researchers conclude. “However, less common adverse effects, such as paranoia and prolonged visual perceptual effects, warrant attention.”
The study authors also push for further exploration via larger trials to fully assess the adverse effects of therapeutic psilocybin use, specifically for populations with comorbid health conditions. They also suggest more research focusing on efficacy of medications, alternative treatments in symptom management and the role of licensed therapists in managing adverse effects.
“Recommendations for solicited acute adverse effects should, at a minimum, include headache, nausea, anxiety, dizziness, paranoia, blood pressure and/or heart rate changes, visual perceptual effects, physical discomfort, and mood changes.”
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