Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome

Summary & key facts

Researchers combined results from many studies to see whether the personal experiences people had while taking ketamine or psilocybin help explain the drugs' benefits for depression or substance use problems. They looked at 23 ketamine studies with about 470 people and 8 psilocybin studies with about 180 people. The personal experiences people reported during treatment explained only a small part of the improvement after ketamine and a larger, but still limited, part after psilocybin. The results suggest these experiences matter some of the time, but they are not the whole story and the evidence is still limited.

Key facts:

• The team reviewed and combined results from 23 studies of ketamine and 8 studies of psilocybin to look for links between how people felt during the drug and how much they improved.
• The ketamine studies included about 470 people in total. Most of those studies were about depression and two were about substance use problems.
• The psilocybin studies included about 180 people in total. Most of those were also about depression and two were about substance use problems.
• When researchers measured how much the subjective experiences explained treatment change, the numbers for ketamine were small. Those experiences accounted for about 5 to 10 percent of the improvement.
• For psilocybin, subjective experiences explained a larger share, about 24 percent of the improvement. That means roughly one quarter of the change was linked to how people felt during the session.
• Across treatments, the link between subjective experiences and benefit appeared stronger for studies of substance use problems than for studies of depression.
• The authors warned the evidence is limited. There were relatively few studies and people overall, so the findings are uncertain. Also, a link does not prove the experiences caused the improvements.

Abstract

There is some evidence that the subjective effects of ketamine and other psychedelics like psilocybin are crucial for their therapeutic outcomes, such as treatment of depression or substance use disorder (SUD). We performed a meta-analysis and systematic review on the correlation of subjective symptoms and dissociation versus ketamine-induced therapeutic outcomes in patients with depression or SUD. A similar analysis was conducted for psilocybin-induced therapeutic improvement. We retrieved 23 papers studying ketamine (21 on depression, 2 on SUD) in 471 patients and 8 papers studying psilocybin (6 on depression, 2 on SUD) in 183 patients. Our study demonstrated a modest role for subjective effects mediating therapeutic outcomes, with R2-values ranging from 5-10% for ketamine and for psilocybine the R2 was 24%. A greater mediating effect for psilocybin compared to ketamine was detected, particularly when restricting the analysis to depression. Additionally there is a greater mediating effect in SUD than depression, irrespective of treatment.

Topics

Chemical synthesis and alkaloids Psychedelics and Drug Studies Treatment of Major Depression

Categories

Clinical Psychology Psychology Social Sciences

Tags

Correlation Geometry Hallucinogen Ketamine Mathematical economics Mathematics Medicine Neuroscience Outcome (game theory) Pharmacology Psilocybin Psychology Therapeutic effect

Substances

Ketamine Psilocybin

Conditions & symptoms

Depression Substance abuse disorder Addiction or harmful habbits Feeling disconnected from others Sadness or low mood