CANNABIS PRECAUTIONS

Cannabis has a long history with humanity, but research hasn’t been allowed for the better part of the last century, and there’s still a LOT that we don’t know. That means there are inherently risks when it comes to consuming cannabis products. Whether those risks are with drug interactions, the consequences of impaired cognition, or even the side-effects of THC, patients should always be aware and take them into account.

Consult a Medical Professional

Always talk to your doctor about cannabis before using it. In Utah you must have a doctor’s prescription to buy, possess, or use cannabis with over 0.3% THC. This is because your doctor knows what other medications you may be on, and any existing mental health conditions that could be exacerbated by THC.

Start Low and Go Slow

Even if you have consumed THC in the past and think you know your tolerance. Anytime you try a new product, take a smaller dose than you think you need, and work up from there over the course of a few days or even weeks.

Put Down the Car Keys

Never drive a motor vehicle or operate heavy or dangerous machinery while under the influence of THC.1

Short Term Cannabis Use

Use of moderate doses in a therapeutic context is rarely associated with severe side effects.2 But cannabis use does have a number of psychological and physiological effects, which can be overwhelming if too much is consumed.3 These include:

• Anxiety or Paranoia • Headaches • Blood pressure changes • Increased appetite • Changes in sensory perception • Memory and judgment impairment • Dry mouth and eyes • Motor and coordination impairment • Dilated pupils • Drowsiness or Fatigue • Facial flushing • Dizziness • Gastrointestinal disturbances such as nausea or vomiting • Distorted perceptions of time and space.

These effects are reversible with cannabis abstinence,4,5,6 but more research is needed to understand their causes and long-term effects. Talk to your doctor about how you might be affected.

Pro Tip: Reach for the CBD

Too much THC can be overwhelming! Luckily, CBD is thought to be a “negative allosteric modulator” of THC. This means it attaches to the allosteric binding site on the CB1 receptor, where it dampens the signal from the active “orthosteric” site where THC docks, thus mitigating the effects of THC.7,8

LONG TERM CANNABIS USE

Cannabinoid Hyperemesis Syndrome

Cannabinoid hyperemesis syndrome, or CHS, was first described in 2004, and still has no clinical guidelines for diagnosis or treatment. This means it is often underdiagnosed, and there is still no real understanding of how or why it happens. What is known, is that for certain people (the jury is still out on whether there is a genetic component), consuming large amounts of cannabis long term (over one year) can lead to severe nausea and vomiting—probably due to the effects such sustained THC levels have on the endocannabinoid receptors. The good news is that symptoms stop when patients stop consuming cannabis, but they can quickly reappear if they resume.9

Hyperemesis Syndrome is a good example of something called the biphasic effect. If you’ve consumed a small dose and had it ease anxiety or nausea, only to consume a larger dose and feel MORE anxious or nauseous than when you started, you’ve felt the biphasic effect. The biphasic curve shows how increasing a dose can increase efficacy up to a point (the optimal dose) but increasing dosage beyond that has the opposite effect.

Cannabis and Psychosis

Cannabis is also believed to exacerbate psychosis in vulnerable people. There’s very little known about how, why, or to what extent cannabis increases the risk of psychosis, but there does appear to be a relationship between early use of cannabis and increased incidence of psychosis later in life. The neurobiological process that leads to this trajectory hasn’t been found, and there are a lot of factors that influence the relationship in both directions, but it’s a strong enough correlation to be taken seriously.10 Research to assess this interaction is ongoing, but in the meantime, it’s important for anyone considering cannabis use to speak to their doctor first, and to discuss with them any heightened neurobiological risks they may have.

Cannabis Withdrawal Syndrome

Since the body desensitizes and retracts receptors with continued THC exposure, ceasing to consume THC can affect the homeostasis of the system.11,12 When this happens, the body’s natural endocannabinoids are not enough stimulus for the depleted receptors, and so the endocannabinoid system’s ability to regulate things like sleep, mood, and pain are affected until the body can regrow those receptors (averaging 10–20 days). This disruption is believed to be the cause of Cannabis Withdrawal Syndrome, symptoms of which include irritability, insomnia, a decreased appetite, restlessness, abdominal pain, headache, or tremors.13,14

Drug Interactions with Cannabis

Enzymes in the liver are responsible for metabolizing around 90% of all pharmaceuticals, including cannabinoids like THC and CBD. These drug molecules interact by either competing for binding sites on the enzymes, or by changing the amount of the enzyme available. Drugs can be either the substrate (the target an enzyme will break down) or the “perpetrator” (acting on enzymes to induce or inhibit them). When an enzyme is inhibited, it metabolizes more slowly, leading to higher levels of the substrate, and longer, more intense effects. When an enzyme is induced, it works more efficiently, clearing away the substrate more quickly and minimizing effects. THC and other cannabinoids can play both roles—either affecting how other drugs circulate, or being magnified or mitigated by them. Always talk to your doctor about how cannabis might interact with other medications you are taking.

THC and CBD may have to compete with other drugs for binding with the enzymes that facilitate their breakdown. CYP3A4 is just one of a few enzymes in the liver known to break down THC and CBD.

Cannabinoid-Enzyme Dynamics

In the liver, cannabinoids may act either as the substrate or as “perpetrators” or when interacting with liver enzymes:

  • Cannabinoids are Inhibiting Perpetrators when they inhibit a liver enzyme to slow the breakdown of a drug. This leads to increased concentration and longevity of the drug.
  • Cannabinoids are Inducing Perpetrators when they induce an enzyme to break down drugs more quickly, leading to decreased concentration and longevity of the drug.
  • Cannabinoids are the Substrate when they are metabolized by an enzyme. Certain medications act as inhibitors or inducers of those enzymes, causing either increased or decreased concentration and longevity of the cannabinoids they metabolize.

References

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    Chemistry & biodiversity, 4(8), 1744-1769.
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