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Cybin: innovating the delivery of psychedelic therapy

The company is investigating novel analogues of psilocybin and DMT to innovate how psychedelic therapies could be delivered.

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Cybin secures patent for psilocybin analogue

CEO of Cybin Inc. Doug Drysdale tells Psychedelic Health about the company’s latest findings on its novel molecules – CYB003 and CYB004.

Cybin has recently announced progress updates for its two lead clinical development programmes.

CYB003 is the company’s proprietary deuterated psilocybin analogue for the potential treatment of Major Depressive Disorder (MDD) and CYB004 is its proprietary deuterated DMT molecule that is being developed for the potential treatment of Generalized Anxiety Disorder (GAD).

Cybin is aiming to revolutionise mental healthcare with these innovative formulations of psychedelic compounds – we speak to Cybin CEO, Doug Drysdale, about the company’s latest data announcement.

CYB003 – novel psilocybin

Interim findings from Cybin’s ongoing Phase 1/2a clinical trial evaluating CYB003 has demonstrated positive observations and the company suggests it may ultimately reduce symptoms of depression after just one or two doses.

Cybin CEO, Doug Drysdale, highlights unique characteristics of the analogue that have been demonstrated in the observations such as a rapid and short-acting psychedelic response in participants, low variability in plasma levels and its ability to induce a psychedelic effect at low doses, while maintaining a safe and well-tolerated therapeutic profile.

For the study, participants received single oral doses of CYB003 at 1 mg, 3mg, 8mg and 10mg, and all doses were well-tolerated with no serious adverse events reported. 

The data also demonstrated that participants reported meaningful and robust psychedelic effects at the 8mg and 10mg doses, confirming that a complete mystical experience was achieved.

“It’s unusual to have a treatment where you can quickly see the effects and when you look across the literature, when you read about people having these very robust psychedelic experiences, or when people will tell you that these experiences fall among the top five most meaningful experiences of their lives, then I think that gets us really excited about what that means in terms of this efficacy study,” said Drysdale.

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“Clearly they have very profound experiences. So, we’re definitely in a phase where we think we’re at the therapeutic dose.”

CYB003 could offer a solution to some of the perceived challenges in implementing psychedelic-assisted psychotherapies in our current healthcare systems.

Traditional psilocybin can last from three to six hours, meaning delivering this therapy in clinical settings will take up a lot of resources, such as staff and therapy rooms. These longer experiences can also make it difficult for some to participate in the therapy due to work and life commitments.

With CYB003 being a fast-acting, short-duration psychedelic compared to a traditional psilocybin experience, the molecule could make the therapy much more cost-effective and accessible for healthcare systems and patients. 

Its novel delivery form may also offer benefits said Drysdale: “It’s an oral – we’re developing a capsule so there’s no need for an IV infusion pump. That makes it really simple to dose. 

“Patients appear to have an onset of effects quite quickly, in 15 minutes or so. Depending on the patient, there are quite robust effects within the range of 30 to 90 minutes or maybe at a couple of hours in that peak state. So, that’s relatively short.”

Drysdale highlights that for some patients with depression, a fast-acting medicine that can see results this quickly is beneficial, as traditional treatments such as SSRIs can take months to work. 

Phase 1 dosing has been completed and the Phase 2a portion of the trial has commenced. Cybin expects to report top-line results from the completed Phase 1/2a clinical trial in late third quarter of calendar year 2023.

CYB004 – novel DMT

Cybin’s DMT analogue – CYB004 – is a scalable and less invasive treatment than traditional DMT. Its Phase 1 CYB004-E trial is evaluating CYB004 in healthy volunteers. 

See also  Animal study shows reduction in chronic pain after psilocybin

The company confirmed in its update that, per a protocol amendment to the initial trial design, it has established a three-part study to include Part A (IV DMT infusion), Part B (IV DMT bolus + infusion) and Part C (CYB004) in healthy volunteers.

This will allow the company to initiate first-in-human dosing of CYB004 sooner than initially planned. Data from the new Parts B and C of the trial will serve to build a more robust pharmacokinetic and pharmacodynamic model to optimise dose selection and formulation development for future clinical studies. 

Part A of the trial evaluating DMT IV in participants is already complete, and IV DMT at the evaluated dose ranges was demonstrated to be safe and well-tolerated. Dosing has now commenced in Part B.

DMT in its native form is not orally bioavailable which means it cannot be delivered in capsule form as CYB003 is.

“What we have done with deuteration is enabled the molecule to be more bioavailable and we have improved the brain penetration,” Drysdale commented. “So, we should be able to formulate that into a small volume that can be given in a more convenient way. This could be intramuscular or subcutaneous injection.” 

“Whereas at the moment we’re studying DMT, and others are as well, using an IV infusion”

IV infusion is not ideal as it requires a line and an infusion pump that needs to be programmed to provide a certain amount of drug over a certain rate of time – needing equipment, a clinical setup and trained personnel – which Drysdale highlights as a major barrier to adoption. 

Cybin’s current study with CYB004 is aiming the understand the right dosing and plasma concentrations, and the relationship between the two and psychedelic effects. A model will be built over the course of the study that will then be translated into a convenient dose form.

See also  Beckley Psytech doses first patients in novel 5-MeO-DMT study

Drysdale said: “One thing we know about DMT is that once the psychedelic effects wear off, it’s cleared from the body fairly quickly. So within 10 minutes or so it’s not traceable. So this could really be a very convenient form for patients and that finally brings them these treatments to the real world.”

Dosing of CYB004 in Part C is expected to begin in early Q2 2023, following the completion of Part B, and Cybin expects to report top-line results from the completed Phase 1 CYB004-E clinical trial in the third quarter of 2023. 

“It is really gratifying to be at this point where, for much of the team who have been working in a lab or working on the more sort of theoretical side of things, to see an idea from a few years ago now being tested in patients,” said Drysdale.

“Around 2000 people die every day from suicide, so this can’t come fast enough. To see the potential for profound effects really quickly is very exciting.”

Join Cybin at PSYCH Symposium

Cybin is a sponsor for PSYCH Symposium: London 2023 which will take place on 6 July at London’s iconic British Museum.

The event will provide audiences with the opportunity to hear exclusive presentations and discussions on stage and to network with leading industry figures.

Cybin’s Chief Medical Officer, Amir Inamdar, will be speaking at the event.

Inamdar is a qualified psychiatrist and pharmaceutical physician with over 20 years of clinical and drug development experience. Previously, he has led clinical drug discovery teams as a medical director for AstraZeneca, Takeda and GlaxoSmithKline.

Get your tickets to PSYCH Symposium: www.psychsymposium.com/tickets

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Is connection key? How clinicians impact patient outcomes in psychedelic therapy

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A wealth of research is showing how psychedelic-assisted therapy holds promise for the treatment of mental health conditions such as depression, but what role does the therapist play in a patient’s outcome? A new study has suggested it may be a big one.

Psychedelics have piqued huge interest due to their effects on the brain. Research points to their ability to induce neuroplasticity in the brain as one of the key reasons they may help with conditions such as depression and anxiety.

However, set – the individual’s (or patient’s) mental state – and setting – the individual’s environment during a psychedelic experience – are hugely impactful on the outcome of these experiences.

In the traditional use of psychedelic medicines, shamans help to guide set and setting throughout the experience with singing, drumming and ritual. Today, in scientific research, trials, and in clinics, the clinician is essentially playing this role.

Senior author of a new study, Alan Davis, associate professor and director of the Center for Psychedelic Drug Research and Education in The Ohio State University College of Social Work, has highlighted that the impact of clinicians on patient outcomes is not new, with research consistently showing that a trusting relationship between patients and clinicians has been key to better outcomes. This concept is known as a “therapeutic alliance”.

Understanding the therapeutic alliance

To find out more about the impact of this therapeutic alliance in psychedelic therapy, researchers from Ohio State University College of Medicine analysed data from a clinical trial that investigated psilocybin-assisted psychotherapy for the treatment of major depressive disorder (MDD).

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In the trial, participants received two doses of psilocybin and 11 hours of psychotherapy, completing a therapeutic alliance questionnaire afterward, which assessed the strength of the therapist-participant relationship.

Participants also completed questionnaires about any mystical and psychologically insightful experiences they had during the drug treatment sessions. In psychedelic research, the mystical experience has often been shown to be related to the continuing positive effects of this therapy.

The Ohio team looked at the depression outcomes alongside patient reports about their experiences with the medicines as well as their connection with their therapists.

They found that a stronger relationship between patient and clinician led to a better clinical outcome for the patient – with improved depression scores up to 12 months following the experience.

Lead author Adam Levin, a psychiatry and behavioral health resident at Ohio State University College of Medicine, stated: “What persisted the most was the connection between the therapeutic alliance and long-term outcomes, which indicates the importance of a strong relationship.”

Analysis results revealed that over time, the alliance score increased, and in fact demonstrated more acute mystical experiences for the patient. The team also found that acute effects were linked to lower depression four weeks following treatment, but were not associated with better depression outcomes a year after the trial.

“The mystical experience, which is something that is most often reported as related to outcome, was not related to the depression scores at 12 months,” Davis stated.

“We’re not saying this means acute effects aren’t important – psychological insight was still predictive of improvement in the long term. But this does start to situate the importance and meaning of the therapeutic alliance alongside these more well-established effects that people talk about.”

See also  First-of-its-kind study to investigate the evolution of psilocybin

According to the team, the analysis showed that a stronger relationship during the final therapy preparation session predicted a more mystical and psychologically insightful experience – which in turn was linked to further strengthening the therapeutic alliance.

“That’s why I think the relationship has been shown to be impactful in this analysis – because, really, the whole intervention is designed for us to establish the trust and rapport that’s needed for someone to go into an alternative consciousness safely,” Davis stated.

“This isn’t a case where we should try to fit psychedelics into the existing psychiatric paradigm – I think the paradigm should expand to include what we’re learning from psychedelics,” Levin added.

“Our concern is that any effort to minimise therapeutic support could lead to safety concerns or adverse events. And what we showed in this study is evidence for the importance of the alliance in not just preventing those types of events, but also in optimizing therapeutic outcomes.”

The authors emphasised that efforts to minimise negative experiences in future studies of psychedelics is vital, and that therapy is critical to creating a supportive environment for patients.

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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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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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