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Psilocybin for major depression trial shows positive results

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Clerkenwell Health calls for volunteers to support groundbreaking psychedelic research

Cybin Inc. has announced Phase 2 interim results for CYB003 – its proprietary deuterated psilocybin analogue – which it says has demonstrated positive results with a rapid reduction in symptoms of major depressive disorder (MDD).

CYB003 demonstarted a rapid, robust and statistically significant reduction in symptoms of depression three weeks following a single 12mg dose compared to placebo, Cybin has stated.

Chief Executive Officer of Cybin, Doug Drysdale, commented: “The overwhelmingly positive interim results for the 12mg dose of CYB003 are extremely encouraging for patients and providers. 

“The efficacy demonstrated at that dosage showed an unprecedented reduction in depressive symptoms compared to currently available treatments.

See also  First patient enrolled in psilocybin trial for demoralisation

“With these encouraging results in hand, we look forward to sharing the full complement of topline data later this quarter, and 12-week durability data in the first quarter of 2024. Our planning continues as we prepare for a larger international, multisite Phase 3 trial in early 2024 to further evaluate the safety and efficacy of CYB003 in people suffering from MDD.”

The Phase 2 clinical trial evaluated efficacy using the MADRS scale. Its primary efficacy endpoint was a reduction in depression symptoms at week three after a single administration. The company has stated that, to date, dosing has been completed in all dose cohorts up to 16mg, with a favorable safety and tolerability profile and no treatment-related serious adverse events observed. 

“These positive interim safety and efficacy results support progressing to pivotal studies. We plan to request an end of Phase 2 meeting with the FDA in early 2024 to align on Phase 3 trial design, and we are commencing dosing with a capsule formulation of CYB003 in the bioequivalence cohort and further manufacturing of GMP materials that will be dose flexible, patient friendly and commercially scalable,” stated Drysdale. 

“This is an exciting time – not only for Cybin, but for the entire psychedelics sector – as we now have interim results showing a significant improvement in depressive symptoms with a single dose, moving us ever closer to delivering on our mission to improve the treatment landscape across the spectrum of mental health disorders.”

Cybin’s Chief Medical Officer, Amir Inamdar, added: “Mental health disorders affect almost 1 billion people worldwide. Comorbid MDD occurs widely in medical and psychiatric disorders, including anxiety disorders and post-traumatic stress disorder. These interim results, together with emerging data from a number of academic studies, suggest that CYB003 may have therapeutic efficacy in range of mental health conditions.”

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Phase 2a trial to investigate 5-MeO-DMT candidate for alcohol use disorder

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Beckley Psytech and Clerkenwell Health are collaborating on a Phase 2a trial investigating Beckley’s synthetic 5-MeO-DMT candidate combined with psychological support as a treatment for alcohol use disorder (AUD).

AUD is estimated to affect around 237 million people across the globe and over 7.5 million people in the UK.

Treatment options for the harmful use of alcohol are not always effective – there are high relapse rates and there are around three million deaths each year attributed to the substance’s misuse.

Increasing research is showing that psychedelics may hold promise as innovative treatments for addiction, including substances such as ketamine and psilocybin.

See also  How psychedelics could help those living with alcohol use disorders

BPL-003 is Beckley Psytech’s short-duration and fast-acting synthetic formulation of 5-MeO-DMT – a psychedelic found in several plant species and the glands of at least one toad species – which is administered intranasally via an FDA-approved delivery device.

The compound has shown in Phase I data to be well-tolerated with a reproducible and dose-linear pharmacokinetic profile.

The Phase 2a trial

Beckley and Clerkenwell have confirmed that the collaborative Phase 2a open-label trial will evaluate the safety, tolerability and pharmacodynamic effects of a single dose of Beckley BPL-003 combined with abstinence-oriented psychological support in participants with AUD.

Currently taking place at King’s College London, Clerkenwell Health’s clinic near Harley Street, London, will provide an additional trial site.

According to Beckley, BPL-003 has been successful in eliciting psychedelic experiences of “similar intensity but shorter duration than psilocybin”.

Dr Henry Fisher, Chief Scientific Officer at Clerkenwell Health, stated: “An estimated 600,000 people are dependent on alcohol in England. This, coupled with an alarming increase in alcohol-related deaths of 89% over the past 20 years, shows the status quo isn’t working.

“Conventional treatments for alcohol dependency aren’t producing meaningful improvements and new avenues must be explored. This trial will assess whether psychedelic-assisted treatment can be an effective therapy for alcohol use disorder, with the hope of rolling out the treatment widely.

“Health professionals and policymakers should seriously consider such treatments, which could be genuinely ground-breaking for the NHS and for the hundreds of thousands of people being treated for alcohol use disorder in the UK.”

Beckley Psytech and Clerkenwell have emphasised that the results of the trial may be used to provide support for further study of psychedelic-assisted treatment for alcohol dependency.

Dr Rob Conley, Chief Medical and Scientific Officer at Beckley Psytech, added: “We’re committed to developing a transformative and effective treatment option for individuals struggling with alcohol use disorder.

“Based on our preclinical and Phase I data, we are optimistic about the potential therapeutic benefits of BPL-003 for substance use disorders and we are excited to evaluate the compound further in this clinical trial.

“I want to extend my thanks to the team at Clerkenwell Health and King’s, as well as to the patients who have joined, and will join, this study. Their participation, support and collaboration are absolutely critical to furthering research into this area of huge unmet need.”

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The Entourage Effect in Mushrooms: Natural psilocybin may outperform synthetic

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The Entourage Effect in Mushrooms: Natural psilocybin may outperform synthetic

A new study from the Hebrew University-Hadassah Medical Center has indicated that natural psilocybin extracts may demonstrate superior efficacy to synthetic psilocybin extracts.

Recent years have seen a boom in research into psilocybin for the treatment of mental health conditions such as anxiety and depression.

Many of the clinical trials investigating psilocybin use synthetic extracts rather than natural ones. This is because synthetic extracts will contain psilocybin alone, whereas natural psilocybe mushroom extracts will contain several different compounds such as psilocybin, psilocin, baeocystin and norbaeocystin.

Having multiple compounds can pose a challenge when running clinical trials as identifying which compounds are active and what their impact is becomes difficult to measure, and the concentrations of these compounds can vary depending on factors such as growth conditions and processing techniques.

This makes the standardisation of multi-compound medicines a huge challenge, as medicine consistency, reproducibility and dosing become difficult. However, these are essential factors when it comes to conducting clinical trials and receiving approval for medicines from regulators.

The Entourage Effect

In 2011 Dr Ethan Russo put forward the theory of the Entourage Effect in cannabis. 

The cannabis plant contains over 400 different cannabinoids that have so far been identified, such as THC, CBD, CBN and CBG.

Russo hypothesised that these different cannabinoid compounds work synergistically to create a therapeutic effect, as opposed to compounds such as THC or CBD working in isolation.

This hypothesis has been touched on only a few times in the scientific literature in relation to psychedelic mushrooms.

For example, in Dr Jochen Gartz’s 1989 paper ‘Biotransformation of tryptamine derivatives in mycelial cultures of Psilocybe’ which proposed a synergistic relationship between compounds in the mushrooms, and a 2015 paper by Zhuck et al, ‘Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice’, which observed that the effect of psychedelic mushroom extracts on mice was much stronger than pure psilocybin.

There has been very limited research on this hypothesis in mushrooms since. 

A new study: Natural may outperform synthetic

Now, a research team from Hebrew University-Hadassah Medical Center BrainLabs Center for the Psychedelic Research have compared a natural psilocybin extract to a chemically synthesised version.

Published in Molecular Psychiatry, results from the study indicate that the natural extract increased the levels of synaptic proteins associated with neuroplasticity in key brain regions, including the frontal cortex, hippocampus, amygdala, and striatum.

The ability of psilocybin to induce neuralplasticity has been indicated as one of the key features that contribute to its therapeutic effects.

The researchers suggest that these new study results indicate that nautral psilocybin extracts may offer unique therapeutic effects that may not be not achievable with synthesised, single-compound psilocybin alone. 

Metabolomic analyses also revealed that the natural extract exhibited a distinct metabolic profile associated with oxidative stress and energy production pathways.

The researchers write: “In Western medicine, there has historically been a preference for isolating active compounds rather than utilising extracts, primarily for the sake of gaining better control over dosages and anticipating known effects during treatment. The challenge with working with extracts lay in the inability, in the past, to consistently produce the exact product with a consistent compound profile. 

“Contrastingly, ancient medicinal practices, particularly those attributing therapeutic benefits to psychedelic medicine, embraced the use of extracts or entire products, such as consuming the entire mushroom. Although Western medicine has long recognised the “entourage” effect associated with whole extracts, the significance of this approach has gained recent prominence.”

However, compared to cannabis, the researchers suggest that mushroom extracts present a unique case, as they are highly influenced by their growing environment such as substrate, light exposure temperature and more.

“Despite these influences, controlled cultivation allows for the taming of mushrooms, enabling the production of a replicable extract,” the team writes.

The researchers emphasise that this research underscores the superiority of extracts with diverse compounds, and also highlights the feasibility of incorporating them into Western medicine due to the controlled nature of mushroom cultivation.

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Ayahuasca retreats associated with increases in nature-relatedness

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Ayahuasca retreat associated with increases in nature-relatedness

A new proof-of-concept pilot study by Onaya Science found that participation in ayahuasca retreats carried out in a traditional Indigenous Amazonian context was associated with significant increases in nature-relatedness.

As highlighted by the research team, anecdotal accounts of ayahuasca experiences commonly describe strong feelings of interconnection with nature. 

“Nature relatedness” – a measure of a person’s relationship with nature – has been linked to improvements in mental and physical health. 

The authors write: “Human connection to nature is being increasingly eroded, partly through increasing urbanisation and a loss of green space, meaning increasing numbers of people are inhabiting nature-depleted environments. This is coupled with shifts in individual behavioural factors such as a greater predominance of more indoor-based sedentary lifestyles and lessened childhood play opportunities outdoors. 

See also  New report analyses amount of people drinking ayahuasca worldwide

“This can result in a diminished potential for everyday interactions with nature or an ‘extinction of experience’, and it has been suggested that this reduced capacity for nature contact and connection has detrimental implications for health, well-being, and propensity towards experiencing positive emotions.” 

The team, led by Simon Ruffell and Sam Gandy, emphasises that, while there is a range of nature-relatedness enhancing interventions such as nature immersion retreats, these may vary in their effectiveness and there is a need for reliable interventions.

Within the context of traditional Amazonian use, ayahuasca practices are deeply rooted in nature and can play a vital role in environmental decision-making. 

Ayahuasca and nature-relatedness

For the study, published in Drug Science, Policy and Law, a group of 43 participants took part in questionnaires both before and after participating in six Amazonian-led ayahuasca retreats at the Ayahuasca Foundation (AF).

The results showed that attendance at the retreats was associated with significant increases in nature-relatedness. Additionally, the team found retreat attendance was associated with improvements in depression and stress, but, not in anxiety. 

The team wrote: “Furthermore, a significant negative correlation with moderate effect size was found between changes in nature-relatedness and stress, suggesting that an increase in nature-relatedness is associated with decreased stress levels after attending Amazonian ayahuasca retreats in our sample.”

However, the team highlights that it is currently not clear whether these reported changes are due to consumption of ayahuasca, or due to the nature-based setting of the retreat. 

“Although this pilot study suggests a potential therapeutic role for Amazonian ayahuasca retreats as a multidimensional intervention, further work is required to assess the role of possible mediators underlying such shifts, while evaluating to what extent these are sustained for long term,” the team writes, suggesting that the findings demonstrate the potential of ayahuasca retreats as a multidimensional intervention that could evoke significant changes in a variety of domains.

The current study did not assess long-term nature-relatedness, however, previous research suggests psychedelic experiences may improve nature-relatedness for up to two years.

Limitations of the study are noted, such as a lack of control group, and factors that may have influenced outcomes. For example, the retreats require participants to disconnect from technology, which may have contributed to feelings of connection with nature, and the inability to carry out constituent analysis of the brew, preventing the comparison of outcomes to the levels of DMT and harmala alkaloids ingested.

Speaking to Psychedelic Health, Gandy commented: “Further research should seek to elucidate to what degree the shift in people’s connection to nature is sustained and reflected in life changes, further explore the specific factors that mediate this shift (i.e. the Amazonian rainforest retreat setting, the Indigenous shamanic context, the ‘digital detox’ or the direct pharmacodynamic effects of ayahuasca) and how it might be enhanced.

“Also, further work warranted exploring the possible additive benefits of a collective, nature-based Indigenous context vs the individualised clinical context: The potential synergistic or additive benefits of the nature-rich Amazonian rainforest retreat setting and other contextual factors such as the disconnection from technology and the nature-orientated shamanic context in influencing nature relatedness in comparison to a Western clinical context warrants further research attention.”

The team concluded: “Whilst our data suggest nature relatedness could be related to changes in mental health outcomes such as stress, our modest, uncontrolled sample does not allow for the generalisation of results. Future studies with larger samples and long-term follow up will shed more light on the initial findings presented in this pilot study.”

The team now plans to run an ‘ayahuasca-free’ retreat following the same structure as a regular ayahuasca retreat but without the ayahuasca brew to investigate the phenomenon while controlling variables.

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Psychedelic Health is a journalist-led news site. Any views expressed by interviewees or commentators do not reflect our own. We do not provide medical advice or promote the personal use of psychedelic compounds. Please seek professional medical advice if you are concerned about any of the issues raised.

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