How a Promising CBD-Based Drug Died

A friend recently asked me about treating a family member with an unusual medical condition: Prader-Willi Syndrome. I did some research and found a pretty interesting story so I decided to share it because it illustrates the strange and fraught ways marijuana-based medications reach the market in the United States.

I am also going to spend a fair amount of time ripping on the pharmaceutical industry so if you’re not into that, turn away.

What’s Prader-Willi Syndrome?

Prader-Willi Syndrome is a genetic disorder where part of a chromosome (lucky number 15) doesn’t work the way it normally does. It produces a range of symptoms. Behavior changes characteristic of PWS include things like temper tantrums and obsessive-compulsive symptoms, and patients often have a mild intellectual disability.

Symptoms vary in intensity. Some Prader-Willi patients live fairly ordinary lives, with well-controlled symptoms and an average lifespan.

One of the trademark symptoms, and one that is often difficult-to-control, is hyperphagia. It means that patients have a compulsion to eat! Sometimes it is so severe that caretakers have to physically provide barriers to food like a lock on the fridge. In the past, PWS patients rarely lived past 50 because of the complications of obesity, but care has improved over the past decades.

Two patients with Prader-Willi Syndrom (aged 2 and 21)

How does marijuana fit in to the picture?

Patients with PWS often end up taking medications for mood control- things like a selective serotonin reuptake inhibitor (SSRI), a common anti-depressive medication. The most effective drugs are anti-psychotic medications, but even in normal patients, these medications almost always cause weight gain.

That puts PWS treatment in a tough spot, because obesity is another one of the issues that PWS patients and families have to think about.

Enter CBD.

CBD has well-known anti-anxiety effects, is well-tolerated with no serious adverse effects, and is not associated with weight gain.

As I have mentioned in other articles, chronic marijuana use is associated with actually associated with a decreased BMI. It’s a little counterintuitive, but this is an observation that has been well-validated for decades! Scientists theorize that it has to do with the way our bodies modulate a hormone call ghrelin, but we really don’t know why that is.

Sad Times with Promising Drugs

It takes a lot of time and effort to develop a drug, so whenever a manufacturer announces a trial related to CBD it represents a huge investment, and that makes us put our hands up in the air and cheer. The more conditions that become treated with marijuana related compounds, the more science we have to back up our industry, and the better we can all feel about life in general.

In 2016, drug manufacturer INSYS announced a trial on CBD and Prader-Willi that would take place in seven American cities (including Tulsa!) This is exactly what we like as doctors. We like multi-center, prospective trials conducted on American populations! In June of 2018, patients started to actually be enrolled.

INSYS is also fairly forward-thinking in other marijuana-related endeavors and had also developed a product called Syndros for tackling issues related to chemotherapy.

Sadly, at the end of the day INSYS is an American pharmaceutical company, and as such, is filled with a bunch of shitheads. By the time the CBD trial started, INSYS was already under fire for illegally promoting a fentanyl derivative called Subsys. They were found guilty of bribing doctors to prescribe this shitty life-threatening medication, because that’s what American drug manufacturers do.

Like the mafia, INSYS was finally upended on federal racketeering charges. In May 2019, numerous members of the company’s leadership were indicted. Later that year, they declared bankruptcy, no doubt hiding money in several dirty little bank accounts in the way most disgraced businessmen do.

Unfortunately, that also ended the CBD trial, and in November 2019, the trial evaluating CBD for Prader-Willi Syndrome was formally ended without results.

At the root of this all is good-ol fashioned American capitalistic greed. Specifically, INSYS’s insistence on maximizing its profit from Subsys, a life-threatening opiate. They got tied up in the opiate crisis and here we are.

The American drug industry will always be hot trash in a sack until America changes the way it prices drugs. The best way to do this is to establish and empower an office of pharmaceutical price regulation. Other industrialized nations have crazy things called a pharmaceutical price regulator. By preventing companies from choosing their own insane prices, we can literally prevent companies from illegally bribing doctors to prescribe opiates, or charging 3k for COVID treatment or whatever evil shit they are doing.

It’s not impossible to do- Canada started their regulatory board in 1987. Just sayin’.

Since the private insurance lobby is the largest in Washington and the pharmaceutical lobby spends at least 250$ million a year, I’m not holding my breath.

Assorted Notes on Studying CBD

One of the trends in marijuana research is that we have a lot more data on CBD than with anything that contains THC. To make a long story short, it’s easier to convince people to let you research a non-psychoactive drug.

This has led to some good things, that I think are ultimately beneficial for the marijuana research community. We kind of think CBD is the effective part of marijuana for a LOT of different conditions- for schizophrenia, for epilepsy, for mood disorders, panic attacks, PTSD and anxiety. This basically cements that marijuana has clinical value beyond its existence as a psychoactive plant- people aren’t just “getting high,” there’s other stuff in there too. There’s a fair amount of clinical data behind CBD at this point.

One of the big issues I have with CBD is the dosing.

For instance, The INSYS study used 40 mg/kg of CBD split into twice-a-day doses. Let’s assume a patient is 100 lbs (45 kg). That means that the INSYS study protocol asks for 1800 mg/day of CBD for this hypothetical patient.

CBD is actually pretty cheap in SOME states (lookin at you oklahoma) where you can get some at a dispensary for 1000 mg for 60$ and that’s a good price. That isn’t even one dose of the INSYS protocol.

A different, current trial, suggests 10 mg/kg/day again split into two doses. That’s 450 mg/day. Still pretty expensive! That amount of CBD is also pretty much guaranteed to taste like dooty if you get it in the cheapest form (elixir/tincture).

Practically Utilizing CBD

The bottom line here is that CBD probably has a lot of benefit for patients with PWS and that dosing it is a huge question mark.

Because of the strange research-consumer mismatch in CBD dosing, I usually tell people that they should be their own test subject for dosing CBD.

I think it’s pretty reasonable to start at a lower dose, like 25 mg/day, and see how it works. Increase to 50 mg/day if you need to, and then 75 mg or 100 mg. There are trials for anxiety and insomnia that show that higher doses (160 mg) are more effective than smaller doses, but lower doses have been shown to benefit patients with anxiety in the past.

CBD is remarkably well-tolerated, with some mild sedation or nausea being the most commonly reported effect. Doses as high as 1500 mg are well-tolerated in the literature. CBD has been described as working immediately- a rarity among mood-altering pharmaceuticals. BUT, I’d still give a trial at least a month of daily treatment.

Another important thing for anyone interested in tackling a mood disorder at home is to have a system for evaluating efficacy. Recording your dosage and symptoms is important to giving CBD a “proper try.”

Feeling better is one thing, but clinical tools like surveys help us give a set number to mood symptoms. If people are tackling anxiety mood symptoms with CBD or marijuana, I often informally recommend filling out clinically-validated survey like a GAD-7 to get a concrete number before and after treatment with CBD. If you start off with a higher score like a 16, and end up with a lower score like a 9, then I’d say CBD has helped you live a better life.

This scale has been used with anxiety patients for years. Is this an evidence validated approach for CBD specifically? Hell no. But it gives structure to something that can be nebulous.

We also have evidence showing that marijuana use (NOT CBD, but THC-containing marijuana) is associated with worsening anxiety symptoms and poor recovery from depression. So, using a survey like a GAD-7 is a good way to make sure you aren’t “tricking yourself” into thinking you’re treating your mood condition with marijuana.

DR LEE