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Non-hallucinogenic LSD derivative reduces depression symptoms in preclinical studies

By Brian Buntz | March 22, 2023

BetterLifeVancouver-based biotech firm BetterLife Pharma (OTCM:BETRF) is working on a non-hallucinogenic LSD derivative for treating neuropsychiatric and neurological disorders.

Known as BETR-001 (2-bromo-LSD), the compound is also not controlled. Conversely, LSD, like other serotonergic hallucinogens, is a Schedule I compound. That status makes it difficult and expensive to research for potential medical uses.

BetterLife announced recent positive results from preclinical studies for the LSD derivative in reducing depressive symptoms in rats.

The research has been published in Cell Reports.

In vitro studies found that 2-bromo-LSD promoted dendritogenesis and spinogenesis in rat cortical neurons. Additionally, in vivo studies found that it produced active coping behavior and reversed chronic stress deficits. Those effects are likely dependent on activation of the 5-HT2A serotonin receptor. The study concluded that 2-bromo-LSD appears to have potential as a treatment for mood disorders and other indications.

Potentially safer alternative to classic psychedelics

BETR-001 is a 5-HT2A partial agonist. In contrast to classic psychedelics, BETR-00t lacks 5-HT2B agonism, potentially making it safer from a cardiovascular perspective. LSD, like other psychedelic serotonergic agonists, interacts with the 5-HT2B receptor, which has been linked to cardiac valvulopathy.

Most of the data linking 5-HT2B agonists to valvulopathy, however, comes from chronic use of medications such as fen-phen, a weight-loss drug popular in the 1990s. A combination of fenfluramine and phentermine, fen-phen, contributed to heart valve damage and pulmonary hypertension in some individuals. Fen-phen, however, has higher selectivity and potency for the 5-HT2B receptor than LSD.

Albert Hofmann, the Swiss chemist who also discovered LSD, also first formulated 2-Bromo-LSD. The compound also has shown promise against cluster headaches. That fact help spark renewed attention in the compound.

In 2021, BetterLife Pharma announced that BETR-001 demonstrated antidepressant activity in a forced swim test with mice conducted at Carleton University’s Department of Neuroscience.

Potential for ‘neuro-psychiatric disorders

In a press release, BetterLife Pharma’s CEO, Ahmad Doroudian, highlighted the potential of BETR-001, stating that the patent-pending compound has “significant therapeutic potential in neuro-psychiatric disorders.” Doroudian also noted that the compound had  an improved safety profile compared with LSD.” The company intends to begin human clinical trials following the completion of IND-enabling studies, hea said.

BetterLife Pharma is also developing a formulation of BETR-001 to treat benzodiazepine dependence, anxiety and spasticity. Additionally, the FDA has provided positive feedback on the company’s pre-IND application for BETR-001 for major depressive disorder.

The company ultimately believes that BETR-001 holds potential for addressing a range of neuropsychiatric and neurological disorders.

The company is traded on three different stock exchanges: the Canadian Securities Exchange, the Over-The-Counter Quotation Board and the Frankfurt Stock Exchange.

Under the ticker OTCM:BETRF, its stock is currently trading at $0.06.

MindMed (Nasdaq:MNMD) is also hoping to develop LSD for mood disorders. The company has received permission from FDA to perform a Phase 2b study of what the company claims is a pharmacologically optimized form of LSD.


Filed Under: Drug Discovery and Development, Psychiatric/psychotropic drugs
Tagged With: BETR-001, BetterLife Pharma, LSD, LSD derivative, non-hallucinogenic
 

About The Author

Brian Buntz

As the pharma and biotech editor at WTWH Media, Brian has almost two decades of experience in B2B media, with a focus on healthcare and technology. While he has long maintained a keen interest in AI, more recently Brian has made making data analysis a central focus, and is exploring tools ranging from NLP and clustering to predictive analytics.

Throughout his 18-year tenure, Brian has covered an array of life science topics, including clinical trials, medical devices, and drug discovery and development. Prior to WTWH, he held the title of content director at Informa, where he focused on topics such as connected devices, cybersecurity, AI and Industry 4.0. A dedicated decade at UBM saw Brian providing in-depth coverage of the medical device sector. Engage with Brian on LinkedIn or drop him an email at bbuntz@wtwhmedia.com.

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