The marijuana plant produces numerous related compounds; the two most abundant are ∆9 THC (tetrahydrocannabinol) and CBD (cannabidiol). THC is responsible for the psychoactive effects, while CBD is non-psychoactive but purported to have beneficial health effects. Specific lines of Cannabis sativa have greater or lesser ratios of these two main cannabinoids. For example, plants with less than 0.3% THC content are grown legally and referred to as “hemp” and are the source of most CBD. Plants with high THC content source recreational and medical marijuana. There is a currently patchwork of THC and CBD legality and availability across the states.
MARIJUANA AND THC
Marijuana with its full range of cannabinoids can be used in many forms including joints, vape, resin extracts, and edibles. The amount of THC in marijuana products varies. An average joint contains 50 to 100 mg, resin extracts can contain upwards of 80% THC, and a serving of commercially-prepared edibles contains 5 to 10 mg. Many states have capped single-serving of edibles at 10 mg THC and the entire container at 100 mg THC.
Adverse effects of marijuana are primarily caused by THC. It stimulates both types of cannabinoid receptors throughout the body. CB1 receptors are located in the brain, GIT, spleen, heart, liver, bladder, uterus, and vas deferens. CB2 receptors are located on immune cells and in the GIT. THC can also influence dopamine, norepinephrine, serotonin, and GABA transmission.
Marijuana-derived products have variable onset and duration depending on their form. Effects from smoked or inhaled marijuana occur in as soon as 5 minutes and last a few hours. Onset from edibles is delayed up to an hour with duration up to 8 hours. THC in the prescription drug Marinol® has onset within an hour and peak blood level in 1 to 4 hours. Elimination is biphasic with a 4 hour initial and a 25 hour terminal half-life.
A WORD ABOUT CANNABIDIOL (CBD OIL, HEMP OIL)
Isolated cannabidiol is available as the prescription drug, Epidiolex®, and was approved by the FDA for certain epilepsies. CBD-oil, also called hemp oil, is found in many forms of non-regulated products, including sublingual tinctures, capsules, gummies, ointments, bath bombs, vaping products, and cigarettes. Although poorly grounded in scientific evidence, CBD is claimed to be beneficial for many health issues including anxiety, insomnia, chronic pain, stress, depression, psychosis, seizures, and immune dysfunction. Adverse effects are limited to somnolence, lightheadedness, mild hypotension, and the possibility of mildly elevated hepatic transaminases.
Caveat Emptor: CBD use will not produce a positive urine drug screen for marijuana UNLESS the product has been improperly prepared and therefore contains THC. Only a minority of CBD products are sold with a guaranteed analysis of less than 0.3% THC.
CLINICAL PRESENTATION OF MARIJUANA/THC INTOXICATION
A mild intoxication, often the desired effect of use, produces euphoria, heightened sensory awareness, altered time perception, silliness, amotivation, increased appetite, and conjunctival injection. More serious intoxications can show lethargy, obtundation, stupor, dysphoria, depersonalization, anxiety or panic, postural hypotension, tachycardia, hypotonia, incoordination, ataxia, slurred speech, and nystagmus. Seizures may be provoked in patients with a seizure disorder.
Children in particular are easily poisoned by edibles. They may also develop respiratory depression that requires intervention.
Patients who use marijuana frequently over a long period of time may develop an peculiar clinical condition called Cannabinoid Hyperemesis Syndrome.
TREATMENT
There is no specific antidote for cannabinoid toxicity. Treatment is symptomatic and supportive.
Liberal use of benzodiazepines may be beneficial for significant agitation or hallucinations.
Obtain routine labs in those suspected of a non-recreational degree of marijuana intoxication. A routine urine drug screen presumptively identifies marijuana/THC, but a positive result correlates only with recent use, and does not diagnose active drug effect.
A FOCUS ON CANNABINOID HYPEREMESIS SYNDROME
This syndrome presents as repetitive cycles of nausea, vomiting, and abdominal pain that persist for 2 to 7 days. Often an extensive and fruitless GI workup is done due to multiple presentations of the patient with these symptoms. A clue in the history is a report that relief is obtained by a very hot shower.
The proposed mechanism is desensitization of the CB1 receptors involved in the central vomiting center. Of note, the responsible neural network also involves the sensory TRPV1 receptor (transient receptor potential vanilloid 1), the same one that is stimulated by hot peppers and hot water.
Treatment of hyperemesis syndrome
Correct dehydration and electrolyte imbalances that result from excessive vomiting. Complete cessation of marijuana use will resolve symptoms, but there are strategies for short term intervention.
Conventional antiemetics such as ondansetron, promethazine, and metoclopramide can be tried but usually have a poor response. As 1st line therapy, apply capsaicin 0.075% cream (OTC product) to abdomen, back or arms, or anywhere the patient indicates that hot water contact gives relief. It may create burning pain, without damaging the skin, but will provide relief of emesis in 1-2 hours. Repeat application in 2 to 4 hours as needed.
Both hot showers and capsaicin may treat symptoms by activating transient receptor potential vanilloid 1 (tRPV1) receptor and bypassing the dysfunctional cannabinoid input.
Adjunctive therapy include sedation with benzodiazepines, antipsychotics, or diphenhydramine. Opioid analgesics are generally discouraged due to lack of efficacy.
If you have any questions about the adverse effects of marijuana, THC, or CBD, please feel free to call the Missouri Poison Center at 1-800-222-1222. Our specially trained nurses, pharmacists, and toxicologist can provide the most up-to-date information regarding exposures and treatment.
