Playing Gummy Roulette

It was, of course, just a matter of time until someone studied exactly what was in the various gummies purchased and passed around like candy. And it's not at all surprising that Dr. Pieter Cohen (1), an Associate Professor of Medicine at Harvard Medical School, who is also the Sultan of Supplements (and maybe even the Headmaster of Hemp and the Vicar of Vitamins), took a shot at CBD Chaos and Melatonin Madness. Alliteration time is now over.

Since CBD madness shows no signs of slowing down (See CBD Oil For Dental Pain? Maybe), let's look at the results of a small 2023 study published in JAMA by Cohen – an outspoken critic of dietary supplements – that evaluates how accurate the labels are for CBD and melatonin content. Short answer: "accurate" doesn't even remotely apply. 

Cohen and his colleagues compared the claimed and measured doses of melatonin (and also CBD) in 30 brands of melatonin gummies. The results are both predictable and horrifying. 

• Only 25 brands met the criteria for inclusion.
• One product contained no melatonin but about 30 mg of CBD per gummy.
• Of the rest, the measured dose of melatonin varied 10-fold, ranging from 1.3 to 13.1 mg of melatonin. (This is an unbelievable level of incompetence and/or sloppiness.)
• When the information about melatonin dose was contained on the label, the variation in the drug ranged from 74% to 347% of the stated dose.
• Of the 25 brands analyzed, only three contained the amount of melatonin stated on the label.
• Five of the products had CBD on the label, but the amount varied by three-fold.

Let's have a poll! Which of the following terms best describes the "quality control" (I can hardly write this with a straight face) used in manufacturing these products:

1. Laughable
2. Laughable but not funny
3. My one-legged poodle could do a better job
4. I don't have a poodle

Fine, pick one, but the real answer here is "atrocious." Can you imagine what might happen if real prescription or OTC drugs, you know, the stuff that supplements fanatics decry as toxic, had such lax "standards?" Here are a few possible outcomes of a 10-fold error in dose.

1. Aspirin: Instead of 325 mg, your aspirin tablets contain 3,250 mg. In one day, at ten times the maximum recommended dose (12 X 325 mg = 3.9 grams), you will have instead consumed 39 grams, easily a lethal dose.
2. Amoxicillin: Instead of 500 mg, amoxicillin capsules contain only 50 mg. The earth will start spinning backward on its axis before your syphilis goes away. 
3. Zoloft (sertraline): The maximum daily dose is 200 mg. At 2,000, there is a very real possibility of a serotonin storm, which is dangerous and can be fatal.
4. Oxycodone: If a pain patient has been taking 10 mg of oxycodone three times a day for a significant length of time and the next batch of pills contains only 1 mg, the resulting sudden withdrawal is very bad news. How bad? Let's ask the FDA. [my emphasis]

Healthcare professionals should not abruptly discontinue opioids in a patient who is physically dependent. When you and your patient have agreed to taper the dose of opioid analgesic, consider a variety of factors, including the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. No standard opioid tapering schedule exists that is suitable for all patients.

FDA Drug Safety Communication, 2019

This borders on hilarious, but in today's world, it's not remotely funny. Ask the millions of pain patients who are taking lower, often ineffective, doses of opioid analgesics how many of them agreed to be tapered and what they're going through as a result. Then, ask the miscreants at PROP for their opinion. Just don't believe a word they say.

Melatonin is not harmless

Since the products studied were, for the most part, inaccurately labeled and the amount of melatonin was generally understated on the label, the possibility for an overdose becomes real. You may say, "It's a natural product that is found in your body, so it's safe," but that's not going to cut it. So is epinephrine (adrenaline). An epi-pen contains between 0.15 and 0.30 mg of epinephrine. Ten times that, and it's bye-bye heart.

This is not to say that fatal overdoses of melatonin are common; it is not especially toxic. But unintentional overdoses are certainly on the rise, and these have consequences.

"During 2012–2021, the annual number of pediatric ingestions of melatonin increased 530% with a total of 260,435 ingestions reported. Pediatric hospitalizations and more serious outcomes also increased, primarily because of an increase in unintentional melatonin ingestions in children aged ≤5 years."
MMWR June, 2022

What we're seeing is simply an extension of the runaway dietary supplement industry with an exception: the look, smell, and maybe flavor of gummies is an engraved invitation for children, who are especially sensitive to melatonin, to consume them in excess. And when the inexcusable incompetence of the manufacturers results in overdoses waiting to happen, this trend cannot be the least bit surprising.

NOTES:

(1) Some of Dr. Cohen's most recent publications (since 2022) on dietary supplements include:

1. Cohen PA, Avula B, Katragunta K, Travis JC, Khan I. Presence and Quantity of Botanical Ingredients With Purported Performance-Enhancing Properties in Sports Supplements. JAMA Netw Open. 2023 07 03; 6(7):e2323879. 
2. Cohen PA, Avula B, Wang YH, Katragunta K, Khan I. Quantity of Melatonin and CBD in Melatonin Gummies Sold in the US. JAMA. 2023 04 25; 329(16):1401-1402
3. Cohen PA, Avula B, Khan I. The unapproved drug centrophenoxine (meclofenoxate) in cognitive enhancement dietary supplements. Clin Toxicol (Phila). 2022 10; 60(10):1156-1158. 4
4. Cohen PA, Avula B, Katragunta K, Khan I. Recalls, Availability, and Content of Dietary Supplements Following FDA Warning Letters. JAMA. 2022 07 26; 328(4):393-395. 
5. Cohen PA, Avorn J, Kesselheim AS. Institutionalizing Misinformation - The Dietary Supplement Listing Act of 2022. N Engl J Med. 2022 07 07; 387(1):3-5. 
6. Cohen PA, Ellison RR, Travis JC, Gaufberg SV, Gerona R. Quantity of phenibut in dietary supplements before and after FDA warnings. Clin Toxicol (Phila). 2022 Apr; 60(4):486-488