As OSP talked to Simon Allen, CEO of clinical-stage biotechnology Anebulo Pharmaceuticals, we asked the question, is marijuana as safe as we think?
According to the National Institute on Drug Abuse (NIDA), there have been no overdose fatalities linked to cannabis alone. The Centers for Disease Control and Prevention also states that while overconsumption of THC may cause emotional distress, extreme confusion, increased blood pressure, severe nausea, heart rate, or unintentional injury, ‘a fatal overdose is unlikely.’
Marijuana is a booming, multibillion-dollar industry, with leading cannabis researcher Brightfield Group revealing that the US market is estimated to reach annual sales of over $31.8 billion by the end of 2023, growing to $50.7 billion in annual sales by 2028.
However, as more states move to legalize cannabis for recreational and medicinal use, the number of marijuana-related emergency room visits are also on the rise.
Specifically, ACI, which can trigger psychosis with hallucinations and includes symptoms such as profound sedation, depersonalization, fear of dying and irritational panic, is a growing issue.
While ACI can cause severe discomfort, it is rarely life-threatening and symptoms generally dissipate within a day. With opioid addiction wreaking havoc across the US, leading to a shocking number of overdoses and deaths, is developing a drug to treat ACI a priority?
Allen certainly thinks so.
“When I pose the question – how many people do you think present to emergency departments around the United States with some form of cannabinoid intoxication every day? The majority of people look at me blankly and say none – what are you talking about?” he tells Outsourcing Pharma at Bio International 2023.
“According to the Nationwide Emergency Department Sample (NEDS), the answer is actually 5,000 people a day, which is 1.7 million a year.”
With the sale of higher-potency THC products on the rise, the Austin, Texas-based company sees a medical need — and a commercial opportunity — for an easily dispensed, high-reversing treatment.
In May 2023, Anebulo announced promising results from its phase 2 clinical trial, despite facing some moral and logistical challenges.
“It’s really not ethical to give healthy individuals massive doses of cannabis, even if they consent. So we started with a low dose and then monitored their symptoms. How high are you? What’s your heart rate? Can you stand still? After one hour, we would then administer either our drug or a placebo,” Allen explains.
Compared to the placebo group, recipients of ANEB-001 experienced ‘significant reductions in a ‘feeling high’ score and THC-induced body sway, plus an improvement on an alertness scale.
“There is no doubt that fentanyl is far more dangerous in killing someone than cannabis is - but the story doesn’t end there. Opioids are used by a very small fraction of people, but with cannabis – we’re looking at 25% of the US population using it on a semi-frequent basis,” Allen continues.
“The legalization and decriminalization of cannabis is taking the US by storm and nobody is really talking about the consequences. These marijuana companies have essentially flooded the market with high potency edibles in many different forms – strawberry, cherry, grape – you name it.”
Unlike cannabis-capital Amsterdam, which has banned the sale of THC products over 15%, the US has little regulation and is now 'routinely' selling 90% pure THC, Allen adds.
“As it becomes cheaper, more potent, and more accessible, ACI cases will continue to grow, putting serious pressure on the healthcare system. We need a solution and I believe Anebulo can provide it.”
Allen also pushes back on the characterization of ACI being something which is 'pleasant or solvable' that can be tolerated and 'washed out' after eight hours.
“If you talk to patients that go through a true ACI experience, it is not a good story. These people are severely compromised, under massive discomfort and quite often very embarrassed about the outcome afterwards. They’ve been known to do all sorts of things, even to the point where they get put in jail. They can become so psychotic that they completely lose control.”
He recounts hearing countless stories from people who have consumed edibles or cannabis-laced brownies, without realising their strength, only to end up in a catatonic state – unable to recall their own name or feel their body.
“When I ask these people if they were able to access a quick, effective antidote, like Narcan for fentanyl, they absolutely would have taken it,” he adds.
There is currently no FDA approved therapy for ACI, with patients simply given a benzodiazepine to calm them down and a beta blocker to slow their heart rate, an approach Allen believes is 'treating the symptoms and not the core of the disease'.
“Doctors don’t have any therapy to treat this – so they will just make the patient comfortable. Patients are often left in a bed for hours and hours to wash out the effects,” he says.
“There is a huge unmet medical need. We believe our drug can provide far better patient outcomes and have a substantial pharmacoeconomic impact.”
In terms of pharmacoeconomics, Allen explains that an individual presenting to the emergency department with ACI will likely be there for six to eight hours, with many cases escalated to the psychiatric ward as the psychosis can become severe.
“With our treatment, an individual may come into the emergency department in a very bad way, only to be stable an hour later – wondering where they are and what on earth happened. Our treatment could free up beds, alleviate the benzos, the beta blockers, and the psych ward – potentially halving or even quartering the pharmacoeconomic impact. We are still going through the numbers depending on how effective our drug is, but that is our intention.”
So, what is next for Anebulo’s drug? While there is still work to be done, Allen is ambitious and hopeful about its future prospects.
The company has a meeting scheduled with the US Food and Drug Administration (FDA) in July 2023, to discuss its phase 2 data and potential regulatory parts.
Alongside clinical trials, Anebulo is also working with Model-Informed Drug Development (MIDD), a group within the FDA that collects clinical data outside of a traditional setting.
“While it’s important to test in healthy normals, it’s also crucial to understand what’s happening in the emergency department. However, you can’t get someone who is intoxicated or incapacitated to consent to a trial. No lawyer is going to let you do that – which is one of the conundrums of ACI,” Allen says.
“With MIDD, after an individual has recovered and can legally consent, we can ask to access their blood work, to understand how much THC was in their blood, how quickly did it clear and any key markers. So we are able to retroactively collect this key information, which we will also discuss with the FDA.”
Looking forward, Allen believes ANEB-001 will be best placed in the emergency department, where the most severe ACI cases are taken. However, he also has a wider vision for the drug to become an over-the-counter treatment and is also considering different routes of administration.
“Our drug has properties that would be very amenable to a nasal spray. Just like Narcan, you use the most convenient route of administration which is useful and quick when someone is essentially unresponsive,” he says.
“While the emergency department is our strategic gateway, less severe or moderate cases of ACI would benefit from ANEB-001. As Narcan has now gone over-the counter, you could see our drug turning up in CVS and Walgreens. There is no reason to believe that, over time, ANEB-001 couldn’t follow the same route.”
As marijuana legalization continues to sweep across the US, the number of ACI cases will likely rise. As they do, Anebulo will be blazing ahead with its treatment – hoping to provide a solution and capitalise on the demand.
