A new study has investigated whether psilocybin could be the key to restore ‘fear extinction’ and thus help treat post-traumatic stress disorder (PTSD).
Fear extinction is understood as ‘a decline in conditioned fear responses’, and PTSD halts this process.
This means that PTSD patients have trouble learning that certain harmless stimuli they associate with a traumatic event or memory pose no immediate threat.
Currently, the mechanisms by which PTSD impairs fear extinction is not fully understood, but some studies have found that patients with PTSD have a smaller hippocampus than healthy people.
It also appears that neuroplasticity, which is the brain’s ability to change and adapt over time, seems to be reduced in the hippocampus of patients with PTSD.
The researchers suggest that, given that this region is involved in memory formation and retrieval, improving hippocampal neuroplasticity may restore fear extinction in patients with PTSD.
With current research around psilocybin – which has been grated breakthrough therapy status by the FDA for the treatment of depression – showing the compound may promote neuronal growth and the formation of new synapses, the research team hypothesised that psilocybin would also be useful for restoring fear extinction by increasing neuroplasticity in the hippocampus.
“Our study is the first to investigate the long-term effect of psilocybin on the facilitation of fear extinction and to assess whether this effect is mediated by the promotion of hippocampal neuroplasticity,” highlights Dr Guyan Wang of Capital Medical University.
Fear conditioning
To investigate their hypothesis, the team induced a sound-based fear conditioning in mice and studied their freezing time in response to the induced fear.
Briefly, the mice were first presented with a harmless neutral stimulus (a 5 kHz tone for 30 seconds) followed by an aversive stimulus (an electric shock to the feet). This setup conditioned the mice to freeze in fear whenever they heard a 5 kHz tone.
Two days later, some of these fear-conditioned mice were administered a single dose of psilocybin and given fear reduction training, which included 12 neutral stimulus fear resolution training sessions.
The mice were then tested for short- and long-term fear resolution as the researchers wanted to see if psilocybin facilitated fear extinction, and if the mice spent less time frozen in fear.
The results showed that psilocybin-treated mice exhibited significantly improved fear extinction compared to the untreated ones.
To understand the possible mechanisms behind their observations, the team dissected and analysed the brains of mice used in their experiments.
They found that the hippocampi of psilocybin-treated mice had dendrites (tree-like structures in a brain cell that receive signals) similar to those of control mice, whereas untreated mice exhibited a sharp decline in dendritic complexity and density.
Additionally, psilocybin reversed the decline in proteins associated with neuroplasticity and fear extinction.
The findings of the study improve understanding of the restorative effects of psilocybin on the brain.
Currently, only two drugs are approved for treating PTSD, both with limited efficacy and severe side effects, the researchers state, thus finding alternative treatments is paramount, and this study may put us one step closer to this goal.
“Collectively, there is increasing evidence suggesting that psilocybin has the potential to treat PTSD. Our findings suggest promising potentials of psilocybin for the treatment of PTSD at the preclinical level and provide impetus for future clinical studies,” concluded Dr Wang.
The study, led by Dr Liming Zhang from Beijing Key Laboratory of Neuropsychopharmacology and Dr Guyan Wang from Capital Medical University, has been published in the Chinese Medical Journal.
