Effects, Side Effects, Adverse Effects

The effects of cannabis can be as variable as the individual patients who use this medicine. There are the therapeutic effects that actively treat either the symptoms or the cause of an unwanted medical condition. There are side effects that occur in addition to those needed for the specific medical condition. Finally, there are adverse effects that are unwanted, sometimes significant enough to require medical attention. 

A desired therapeutic effect for one patient may be an undesired side effect for another. For example, one patient may be using medical cannabis to increase appetite. Another patient may be using medical cannabis to treat chronic pain while also trying to lose weight. In this situation, increased appetite is the desired therapeutic effect for the first patient while increased appetite becomes an undesired side effect for the second patient. Some possible side effects, such as feeling faint or dizzy, are generally undesirable for all patients.

The effects of cannabis are primarily caused by the cannabinoid and terpene content in the variety being used as medicine. Each cannabinoid has unique effects, terpenes bring their own effects, and together they create what we know as the therapeutic entourage effect.

In addition to the plant constituents, a patient’s individual physiology, metabolism, and experience with cannabis will also contribute to the effects of the medicine. A patient who has never used cannabis, or one who has not used it for a period of time will have a different response than a patient who is using the medicine on a regular basis. With regular use, tolerance builds to the intoxicating effects of THC, a development called tachyphylaxis. Tachyphylaxis can be helpful when higher doses of THC are needed, allowing patients to slowly titrate up to acceptable levels without debilitating side effects.

Effects also depend on the delivery method used. For example, smoking is much more likely to cause throat irritation and coughing than ingesting a capsule. Ingesting is much more likely to cause longer-lasting effects than inhaling causes.

Evidence-based information on the effects of specific cannabinoids and terpenes is limited. However, both evidence-based and anecdotal reports have identified the following effects.

 

Generally Therapeutic

  • Increased appetite
  • Pain relief
  • Relaxation and calming, anxiolytic
  • Drowsiness, lethargy (sleep aide)
  • Euphoria, giddiness (anti-depressant)
  • Anti-spasmodic
  • Seizure control (cannabinoid specific)

possible side effects

  • Increased or decreased sociability
  • Feeling faint, dizzy, or lightheaded
  • Headache
  • Slowed or impaired memory and cognition
  • Lethargy (inappropriate)
  • Disorientation, confusion, feeling extreme slowing of time
  • Impaired motor skills, perception, and coordination
  • Suspiciousness, anxiety, paranoia, hallucinations (dose-dependent)
  • Dry mouth
  • Throat irritation, coughing (with smoking)
  • Higher or lower blood pressure levels
  • Abnormally fast or slow heart rate
  • Interactions with other medications
  • Nausea, vomiting
  • Worsening of seizures (cannabinoid dependent)

Possible adverse effects

  • Chronic bronchitis (with smoking)
  • Cannabinoid hyperemesis
  • Possible increased risk of heart attack

Psychoactive vs. Intoxicating

Any substance that crosses the blood-brain barrier, altering brain function, is psychoactive. Coffee, cigarettes, beer, and sleeping pills are all psychoactive. Cannabis is a psychoactive medicine simply because cannabinoids bind to receptors in the brain. In contrast, intoxication is when psychoactive substances cause disturbances in the level of consciousness, cognition, perception, judgement or behavior. THC causes intoxication and CBD does not. Of the over 100 cannabinoids in cannabis [1], THC is the only one that causes significant intoxication. The form of THC in raw cannabis is THCA (an acidic form) and this is not intoxicating. But when the plant is dried and heated, THCA is changed to THC. When considering possible side effects of a cannabis variety, one must consider the amount of THC, and the amount of THCA that will become THC when processed. Intoxication can be a therapeutic effect for some, and an unwanted side effect for others.


Adverse Effects

Cannabis is not good medicine for everyone. While cannabis has no fatal side effects, there are a few possible serious adverse effects that occur infrequently, but often enough to mention here.

 

Cannabinoid Hyperemesis

Cannabinoid Hyperemesis is a condition in cannabis users that causes severe nausea, vomiting, and abdominal pain. It was first identified in 2004 in Australia after 9 patients had presented to the emergency department with these symptoms. The only way these patients could find relief was by taking hot baths, some of them to a pathologic degree. The physiologic cause of the problem has yet to be identified, but there may be a clue in the ‘hot bath’ phenomenon. We know that activated CB1 receptors cause vasodilation in the gut, and hot water causes vasodilation in the skin. To some patients sensitive to the gastrointestinal effects of cannabis, increased GI blood flow may cause nausea, vomiting and pain. Redirecting the blood to the skin would relieve the congestion in the gut, relieving the vomiting and pain. Avoidance of cannabis is the definitive treatment of cannabinoid hyperemesis. [2]

 

Cardiac Risks

In 2001 it was reported the risk of having a heart attack was increased by 4.8% for an hour after using cannabis. [3] The mechanism for this rare but increased risk was not identified, but to some it made sense. Cannabis causes increased blood pressure when lying down, and decreased blood pressure when standing up. It can also increase the heart rate. But we would expect that if the risk of heart attack is increased after using cannabis, then the increased use of cannabis since 2001 should have led to an increased incidence of heart attacks. We have not seen that trend, and since then, we have learned more about cannabis and its effect on cardiac tissue, including some cardioprotective effects. [4] More recent data puts the increased risk of MI at 0.8%, less than that caused by air pollution. [5]  However, it would be prudent to consider the possible effects of cannabis on patients with known cardiovascular disease.

 

Overdose

While there are no records of cannabis-related overdose fatalities, it is possible to overdose and have severe undesired effects. These effects pass within a few hours but can be very unpleasant while they last.  Patients have reported heightened disabling anxiety, catalepsy (inability to move), and extreme disorientation.

Note: those who experience chest pain or a severe, intolerable adverse effect should contact a healthcare professional.

Although it is a potent drug that may produce intoxicating effects, THC (and the other cannabinoids) have relatively low toxicity, and lethal doses in humans have not been described. A human would have to consume 20,000 to 40,000 times the amount of cannabis contained in one joint, in a short period, to achieve lethality. Using this as a basis, it has been estimated that it would require 1500 pounds of cannabis smoked in 15 min to induce a lethal effect. [6]

 

Long-Term Side Effects

As with effects and side effects, there is limited and conflicting clinical evidence on the long-term side effects of cannabis use. Long-term side effects can include:

  • Increased risk of triggering or aggravating psychiatric and/or mood disorders including schizophrenia, psychosis, anxiety, and bipolar disorder, particularly in adolescents.
  • Increased risk of developing chronic bronchitis (with smoking).
  • Decrease in efficacy of one or more cannabis compounds by developing a tolerance.
  • Psychological dependence/addiction characterized by impaired control over drug use, compulsive use, continued use despite harm or lack of benefit, and craving.
  • Positive long-term side effects include continued efficacy of the medicine if used appropriately and dose-adjusted for tolerance.

Sources

  1. Lumír Ondřej Hanuš, et al, Phytocannabinoids: A Unified Critical Inventory; Nat Prod Rep 2016 Nov;33(12):1357-1392   DOI: 10.1039/C6NP00074F

  2. J Am Board Fam Med; November-December 2010; vol. 23 no. 6 790-793 0.3122/jabfm.2010.06.100117[1]

  3. Mittleman, M.A. et al: Triggering Myocardial Infarction by Marijuana. Circulation. 2001; 103: 2805-2809

  4. Russo Ethan: Synthetic and Natural Cannabinoids: The Cardiovascular Risk. Br J Cardiol 2015; 22:7-9

  5. Nawrot TS, et al. Public health importance of triggers of myocardial infarction: a comparative risk assessment. Lancet 2011;377:732-40

  6. Young F: In the Matter of Marijuana Rescheduling Petition. US Department of Justice, DEA (1988):Docket No 86-22.