The decision to move from a system in which cannabis is completely illegal, to one in which it is not only legal for recreational use, but also facilitated with government resources, has many implications in many realms. Advocates point to significant gains in the social justice arena and the relative safety of cannabis over other drugs like alcohol and opioids. Economic benefits in terms of tax and commercial revenue are impossible to ignore. Arguments abound regarding how common cannabis use is already and liken our current state to Prohibition-era alcohol laws. Opponents voice concerns about the expansion of social ills like homelessness, joblessness, and crime, and turning once prosperous cities into a scene from the Walking Dead.1 How can we convince our nation’s youth to not abuse cannabis when it’s legal….and, in many cases, a medicine? (So, how can it be bad?) What will be the effect on public health? Will there be more marijuana addiction? Will there be more motor vehicle collisions? Will there be poisoning? (Of course, there is always poisoning) Will there be . . . reefer madness????
It’s this last realm that I will try to untangle from the viewpoint of a medical toxicologist – the adverse health effects. Anytime a drug is introduced – whether it is a pharmaceutical or a recreational drug – there will be adverse events. It’s our job to know what they might be so we can anticipate them, respond to them, and – wherever possible – prevent them.
Cannabis legislation is changing quickly in the United States, with more states voting to increase cannabis access every year. As of November 2018, there are 11 states with legalized recreational programs and over 35 with medical marijuana. What’s the difference? Medical marijuana implies a tightly regulated, state-run program, in which patients can only obtain medicinal cannabis products for one of a list of approved indications. A physician or other provider must document the indication and details of marijuana therapy, and the patient goes to a designated dispensary, often assigned based on county or municipality of residence. Decriminalization is a stepping stone on the cannabis access journey, and reduces or eliminates penalties for cannabis-related offenses – but there is no state-regulated industry to license (and tax) cannabis commerce. Legalization is the most liberalized access to cannabis that states can choose, and in addition to making adult-use recreational marijuana legit, it establishes a framework for the licensure, enforcement, and taxation of cultivators, processors, wholesalers, and retailers.
What is Cannabis?
Let’s turn to the chemistry and pharmacology. “Cannabis” is the term used to refer to alkaloids of the Cannabis sativa and C. indica plants, indigenous to Southeast Asia, but grown all over the world. Although the plant yields a number of alkaloids, the two primary actors are delta-9 tetrahydrocannabinol (affectionately called “THC”) and cannabidiol (CBD). THC is the reason people use recreational cannabis – it confers the desirable psychoactive effects of relaxation, euphoria, and giddiness that cause uncontrollable giggling. CBD, on the other hand, has minimal psychoactive effects and is taken for perceived benefits in a variety of medical conditions, ranging from pediatric epilepsy to insomnia.2 In New Jersey, CBD is sold over the counter and is not what is meant by the term “Medical Marijuana”.
Also NOT included: synthetic cannabinoids, also known as K2, Spice, #NOTpot (but please, not “fake weed”). These are compounds synthesized initially to study the cannabinoid receptors CB1 and CB2,3 which went terribly wrong when released onto the drug marketplace and have been responsible for everything from zombie outbreaks to fatal coagulopathy (listen here). Buyer beware, and stay away!
Natural cannabis alkaloids stimulate receptors all over the brain as part of the endocannabinoid system. This is a funny thing: there is already circuitry in place to specifically capture the effects of cannabis on the brain. Why? Probably not so humans can enjoy smoking pot, but because there are endogenous cannabinoids (anandamide, for example) that mediate important activities like temperature control, appetite, immune response, complex movement, and higher cortical function. So, introducing exogenous cannabis hijacks this homeostasis. Some have raised concerns about the effect of this disruption, particularly on the developing brain. Nonetheless, endocannabinoid receptors (CB1 and CB2) throughout the brain mediate a variety of effects on mood, cognition, and coordination. Interestingly, the absence of cannabinoid receptors in the brainstem is the reason used to explain why cannabis overdose does not cause respiratory arrest (except, maybe, in children).
The Dose Makes The Poison
As numerous as these receptors are, there are also countless formulations of, and methods to use, recreational cannabis. The bud, or flower, is most familiar and is the botanical leaf product generally rolled into a joint or smoked in a pipe, and is still going strong. Stronger than ever, in fact – the THC concentration in the bud of yesteryear was around 1-3%, whereas today it is closer to 20%.4 This takes many an unsuspecting user by surprise, as the effect previously achieved by smoking an entire joint might now come from just one hit. Beyond that, the cornucopia of liquids, oils, waxes, resins, and – of course – edibles, abounds. Although terminology varies, concentrates generally refer to highly concentrated liquids which may be used in a vaporizer or vape pen, ingested, or included in an edible recipe to ensure a homogenous distribution of THC (instead of a clumped cannabis cookie with one very tricky, THC-rich corner). A concentrate is produced by crushing the leaves and creating a solution of the active ingredients (in water, oil, or alcohols), but does not use a heat-extraction process, or volatile organic solvents, like butane or propane. In contrast, an extract also starts with the botanical product and removes the alkaloids, but this is accomplished by soaking the crushed leaves in a solvent, then heating the solvent until it largely evaporates, leaving behind a waxy substance with a THC concentration that may be as high as 90%. Unfortunately, the whole “heating a volatile chemical” thing can get tricky – so things blow up, and people get burn injuries.5 Extracts go by a lot of names, including “wax”, “dab”, “amber”, “shatter” when in the solid or semi-solid resinous form, and can be ingested or inhaled. Lastly, edible products can be commercially produced (gummy bears) or homemade treats (brownies, cookies, etc), and are prepared using any of these precursors.
How much is in a “serving size” of each is harder to say. Generally, a “hit” of the smoked bud is around 2 mg, and a single dose of edible is between 5-10 mg. A medicinal edible may contain as much as 100 mg per serving. Concentrates may contain as much as 1000-4000 mg per bottle. How much is too much? Generally, toxicity is experienced around 5 mg of THC/kg in cannabis-naïve children, and higher than that in adults.6
Another aspect of this formulation bonanza is the different pharmacokinetics and route of administration of the various products. Inhaled THC achieves a measurable plasma concentration almost immediately, and the effect is felt very soon thereafter. It peaks in an hour or so and wanes over the next 3-4 hours. Users can self-titrate by taking additional puffs when needed, and backing off if the effect is too strong. This is why few people poison themselves by smoking marijuana (unless it is unexpectedly concentrated). In contrast, ingested cannabis takes an hour or more for the effects to be felt, the peak occurs in 2-3 hours, and effects can last up to 24 hours.7
Naïve users may eat more than they should while waiting for the first dose to take effect. This dose-stacking process was chronicled by NY Times columnist Maureen Dowd, who flew to Colorado to be a “marijuana tourist” and spent an exceedingly unpleasant 24 hours in a hotel room after ingesting 16 doses from a cannabis granola bar.
The Health Consequences of Legalization
A lot has been written about the potential health effects, both positive and negative, of cannabis. In general, the research on positive effects centers around the use of medicinal marijuana, and the safety considerations/adverse effects around recreational cannabis. The list of medicinal indications is long, some with stronger evidential support than others.
Recreational cannabis will likely have at least one benefit to users because the product being sold in the legalized framework is “cleaner.” Analytical testing can be performed on products before sale, to confirm the presence and concentration of cannabis alkaloids (THC, CBD, Cannabinol, and others), and the absence of unwanted contaminants like pesticides, solvents, Aspergillus and other mold spores, bacteria, and heavy metals. The product is labeled as such and consumers can use judiciously based on labeled concentration and contents.
The adverse health effects range from the established to the theoretical (albeit concerning). We do know that more adults and children will have cannabis toxicity that results in a call to the PCC and possibly an ED visit.8,9 Adult patients will generally be uncomfortable, but not in danger: flushed, tachycardic, anxious, even panicky, but the effects will wane over a few hours and resolve in the vast majority of cases. Risk factors for these cases include naïve users and exposure to edibles.
Kids Are Diff’rent
Pediatric poisoning, however, is a different story, particularly in young children.
Case: A 2-year-old girl finds a bag of 10-mg cannabis gummies and eats approximately 15 of them. She becomes somnolent and her father calls 911. En route to the hospital, she has a seizure. On arrival, her vital signs are normal except for tachycardia, but she is very lethargic. She develops respiratory depression and has to be intubated, and spends 2 days on the vent. She recovers without sequelae.
Can this happen? Yes. Does this happen? Yes. As hard as it is to believe, the “nobody dies from marijuana” adage may, in fact, be an oversimplification. A child eating a high dose of THC can develop respiratory depression or even apnea.10 The dose at which that occurs is hard to pin down but is estimated to be at or around 7 mg/kg.6 Considering the amount of THC in some of the highly concentrated liquids (4000 mg in one product!) – the potential is real. These cases are almost all ingestions and include commercial edibles, homemade edibles, concentrates, and waxes/resins. Homemade edibles are an interesting hazard here – parents are probably much less likely to lock up their batch of freshly made brownies than their vaping liquid.
Beyond poisoning, there are quite a few other considerations where evidence is evolving (and beyond the scope of this discussion): effects in pregnancy and lactation, adolescent substance use and abuse, existing and emergent mental health conditions, driving safety and what to do about it, the influence of heavy cannabis use on long-term socioeconomic status and IQ….the list goes on and on. Suffice it to say that several organizations have conducted thorough reviews on these, with statements reflecting the state of the evidence on each.
So how do we proceed?
There are a few no-brainer, let’s-prevent-poisoning answers here:
- Testing and clear labeling of commercial products for contents and concentration. An educated consumer is the best customer. https://en.wikipedia.org/wiki/Syms_Corporation (obligatory Jersey shout-out)
- Dose size limitations: the milligrams of THC allowed in a single serving size of recreational cannabis. These range in established states from 5-10mg.
- Pack size limitations: a related concept which limits the number of doses/serving sizes in that Maureen Dowd granola bar.
- Down with look-alikes. A lot went awry in the early legalization days, as retailers sold products that were direct mock-ups of popular treats, like “Pot Tarts”, “Stoney Ranchers”, and a variety of favorite candy bars. This flies in the face of everything we know about poison prevention: don’t make drugs look like candy, or children will eat them. There are vanishingly few pharmaceuticals that are packaged as food, and with good reason. You can’t buy metoprolol lozenges or coumadin cookies. Why should this be different?
- Other packaging details: Child-resistant, 2-mechanism resealable closures, and opaque packaging. Warning labels (like “Not for children!”) which are large, colorful, and clear – and which rotate regularly to avoid overexposure – and diminish the “yeah, yeah” response.
In the long-term big picture, we’ve got to keep our eyes open. There are more questions than answers, and research is needed in all corners of the issue. We know there will be myriad public health effects, and toxicosurveillance is essential to identify hazards as they arise. We can’t manage what we don’t measure. Poison Control Centers are a natural solution to this need for real-time surveillance, and can also carry out the necessary public and professional educational outreach a change like this requires.
But opinions aside, it’s our job to know what is known, detect the as-yet-unknown, and prevent the preventable.
- The Dantastic Mr. Tox & Howard – S03E03 – Inside Out - July 6, 2020
- Tox and Hound – Love and Half-Life* - February 26, 2020
- Tox and Hound – One Therapy To Rule Them All? Sugar vs Squeeze in Cardiotoxic Poisoning - February 18, 2020