Synthetic cannabinoids and cathinones

Spice, K2, Bath Salts – vicious, nasty drugs

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A patient came into our addiction clinic who was homeless and desperate for treatment for her opioid addiction. We readily treated with a dose of methadone and set her up with an ongoing program. She had no interest in addressing the other addiction she had – to K2, or Spice, a dangerous and wildly unregulated synthetic cannabinoid (cannabis-like molecule). She was buying Spice on the streets daily, a small bag for five dollars. She was smoking it every night at bedtime. After consuming, she was able to sleep for 4-5 hours, but she would then, in the middle of the night, start to viciously withdraw in the early mornings. When withdrawing, she experiences shaking, nausea, severe anxiety and panic. In response, she would consume more fentanyl to calm things down (a life-threatening technique to calm oneself down…) and go out to buy more K2 from her dealer – a downward, dangerous, and depressing cycle. At this point, without K2 she can’t sleep at all, though she felt little euphoria and had little pleasure from smoking it. She now suffers daily from anxiety, irritability and poor appetite from the cycle of binge/withdrawal cycle. She feels hopelessly trapped in this cycle because of her untreated anxiety and because of the brutal withdrawal symptoms.

Separately, I remember watching a video of an obviously impaired teenager, who couldn’t have been more than sixteen years old, smoking a cigarette as he was sitting in the police station. He was clearly psychotic, and on the wrong side of the law. There was no actual cigarette in his hand, but the kid was under the illusion that he was smoking. He even politely tapped the ashes into a paper cup so as not to sully the floor of the detention room he was in. Once done, he snuffed out the imaginary cigarette. He was under the influence of bath salts.

What are synthetic cannabinoids/bath salts?

Bath salts represent a category of illicit drug that contains combinations of various synthetic cathinones, including the major ones MDPV, mephedrone, and methylone. In the same category, but potentially less toxic, is an alkaloid derived from east Africa's khat plant, has been chewed by people for hundreds of years for its stimulant effect. In the U.S. bath salts are considered a “legal high” even though that isn’t always the case. It depends on which bath salts you use (some have been banned), and most others are found, at best, in the gray market. They are difficult to detect on drug testing.

K2/bath salts/synthetic cannabinoids tickle the same receptors that cannabis does. Synthetic cannabinoids can impact these receptors in a manner that is stronger and longer acting. At low doses, people often report effects that are similar to cannabis, such as relaxation, euphoria, enhanced appreciation of music, and hunger.

But at even slightly higher doses, or if people get a bad batch of synthetic cannabinoids (which is extremely common – see below), they can have awful side effects including paranoia, terrifying hallucinations, heart attack, psychosis, self-destructive and violent behavior. There have been numerous deaths from the use of bath salts.

Synthetic cannabinoids also cause a vicious withdrawal syndrome. Abrupt discontinuation of daily synthetic cannabinoids has been associated with severe anxiety and insomnia (such as with the patient mentioned above), as well as seizures and cardiovascular and respiratory risks, such as tachycardia, chest pain, palpitations, dyspnea.

Sounds like fun, doesn’t it? Why don’t people just stick to weed?

Astoundingly, according to a detailed poll of synthetic cannabinoid (SC) users,

The majority of users reported disliking SCs (56.4 %), with 7.5 % reporting a strong dislike for the drug. A subset of respondents (15.4 %) reported liking the drug, and 17.3% provided a neutral response or no response.

Given how dangerous and unregulated these drugs are, how grievous the side effects and the withdrawal can commonly be, and the fact that most people don’t even enjoy taking them, why the fuck to people even use synthetic cannabinoids? Only 15.4% of the users reported actually liking the drug. Do people try them and just get so addcited that they have to keep consuming?

The majority of synthetic cannabinoid users tend to be cannabis users, though they represent a tiny majority of cannabis users. Perhaps - and I am speculating here, they just are bored and anxious, or desperate people who want that extra boost of the cannabinoid system, more than simple weed can give you. My patient above stated just this: that she found cannabis wasn’t strong enough to alleviate her anxiety and insomnia. Sometimes with drugs, people believe that more is better. (Sometimes it is…depending on what you wish to accomplish, but not in this case!)

To all of this I say no thanks!

Synthetic soup

Part of the problem with synthetic cannabinoids is that they aren’t a homogenous group of substances. They are a completely unregulated mixture of a potentially wide range of chemicals, some dangerous and some even more dangerous. As mentioned, the main ones are MDPV, mephedrone, and methylone. The composition and dose of bath salts can vary tremendously, making diagnosis challenging and leading to greater risks of overdose and adverse reactions, or drug reactions. It can be hard for the E.D. staff to know what drug people are coming in on. With the production and distribution of bath salts, there is no adult in the room, no standards for purity or safety, no regulation of dosage, labeling or packaging. It is the Drug Hunger Games.

Due to growing concern about rising rates of E.D. visits for synthetic cannabinoids, President Obama signed a 2012 law that placed dozens of synthetic cannabinoids and cathinones into Schedule 1 of the Controlled Substance Act, including the main ones listed above. This is the most restrictive category that cites “no medical use” and “high abuse potential”. Of course, with these chemicals locked away under Schedule 1, it remains difficult to study if there is medical use for them. Some synthetic cannabinoids are used fruitfully in the lab to help us unlock the mysteries of the endocannabinoid system, but these tend to be molecules created for, and kept in, the laboratory.

As discussed in many of my blogs, the War on Drugs method of drug control – locking everything away with huge criminal penalties for using – doesn’t work very well. Despite the Obama-era reclassification, people can readily purchase bath salts on the Internet and in retail stores, camouflaged under names such as stain remover, research chemicals, plant food, and insect repellent (or just “bath salts” which is where they get their name.)

It isn’t as easy to obtain them as it was before this Obama-era reclassification. For example, you can’t really procure them at gas stations or smoke shops anymore, which is an improvement but, if you know what you are doing, they are freely available on the internet or on the streets.

How do they affect us?

Regular cannabis (and bath salts) works on the endocannabinoid system (ECS), which is described in detail in a previous blog. The ECS is the network of neurotransmitters and receptors upon which cannabis, or our natural endocannabinoid transmitters, act on to work their effects. Our natural endocannabinoids moderate a wide range of critical physiological processes such as learning, memory, pain processing, sleep, appetite, temperature control, and reproduction. They keep our bodies in balance, or in “homeostasis”, by acting as a sort of switchboard operator for our other neurotransmitter systems. The synthetic cannabinoids, such as K2, can stimulate the cannabinoid receptors in our brains thousands of times more efficiency than our natural cannabinoids do, which is why they are so toxic.

How do you treat?

As with all drug misuse, the first steps are education. These drugs are profoundly dangerous, unregulated, and they don’t even seem to be particularly enjoyable. The next step is regulation, which is difficult to do because they are sold in the illicit market, and newer cathinones are being developed all the time, so outlawing them is like playing ‘whack-a- mole’.

If a person is dangerously intoxicated on bath salts, psychotic or panicked, smoking imaginary cigarettes and such, the treatment is largely supportive. In the Emergency Department they can give benzodiazepines (Valium, Ativan, Clonapin) to calm them down. If they have psychotic features (such as delusional cigarettes or paranoid fantasies) they can give them antipsychotic medications. They can treat any other physical consequences such as headache, heart attack, stroke, or vomiting. They can give intravenous fluids to help support the cardiovascular system.

For withdrawal, which can be extremely severe, there is no medical protocol yet for this. For other drugs, we try a gentle taper, but these are way too dangerous and unregulated for us to give to people even in this context. We don’t have synthetic cannabinoids that we can prescribe. We rely on supportive care as above.

I wonder if they should study the use of cannabinoids, such as THC and CBD, in the treatment of withdrawal from bath salts, as a much safer way to foster gentle withdrawal. These compounds much more safely trigger the endocannabinoid system. Before this happens, the addiction psychiatry community, and the conservative, Drug War-ey elements of the U.S. Government, would have to get over their collective neurosis about cannabis and come to accept it as the relatively non-toxic plant-based medicine that most other people are accepting it for.

Conclusion

If you want to stimulate your endocannabinoid system, stick to the herb! Avoid these nasty chemicals unless and until there is a future point when they are proven to be safe, legally sold, regulated, and when you know exactly what dose and product you are getting. In that future scenario, we could theoretically harness the medical potential, if there is any, of these dangerous and unregulated drugs that are harming so many.

References:

1) Article in JAMA: https://jamanetwork.com/journals/jama/fullarticle/1486827

2) Spectacular article by Dr. Ziva Cooper: https://pmc.ncbi.nlm.nih.gov/articles/PMC4923337/