Cannabis & Drug Tolerance

Drug Tolerance / Drug Insensitivity

When an individual develops a diminished response to a drug following a period or repeated use. Often this is the result of prolonged use of a drug causing one’s body to adapt to the constant presence of the substance.

Classes of Drug Tolerance

Dynamic Tolerance: Adaptive changes to receptor sites in the brain.

Dispositional Tolerance: Changes in how a drug is absorbed by the body.

Behavioral Tolerance: Administration environment familiarity.


It is not uncommon for individuals over time to develop tolerance to a medication, resulting in a drop in the effectiveness of symptom management from their prescribed dosage. This can occur through a change in how the body metabolizes a drug, or in the case of cannabis medicine, changes in cell receptors within the body (CB1 receptors).

Common medications that are associated with drug tolerance/insensitivity also include:

  • Opioids
  • Antidepressants
  • Antibiotics
  • Anxiolytics
  • Chemotherapy drugs

In the case of cannabis medicine, tolerance is most commonly associated with patients who are consuming doses with a high potency of delta-9-tetrahydrocannabinol (THC) over an extended period of time. Tolerance can also be affected by one’s gender, DNA, pervious use history, and drug delivery method.

Cannabis tolerance is caused by the downregulation of the body’s CB1 receptors. The regular presence of THC in the body can inhibit CB1 receptor sensitivity, and reduce the number of CB1 receptor sites available for binding through receptor internalization.

In the short term, patients can benefit from an increased tolerance to THC through a reduction in potential unwanted side effects such as intoxication or psychomotor impairment. However, over time this tolerance can also lead to a limiting of the sedative and pain-relieving effects of THC.

Additionally, prolonged use of THC dominant cannabis medicine can potentially also result in increased synthesis of pregnenolone in the brain. Increased levels of this hormone might ultimately result in limiting the effects of THC by acting as a signal inhibitor for the CB1 receptor.


Mitigating Cannabis Drug Tolerance

When discussing medical cannabis and drug tolerance, it is important to note that this downregulation of the body’s CB1 receptors is associated with THC consumption and not cannabidiol (CBD). Current research suggests that the consumption of CBD does not result in CB1 downregulation or an increase in drug tolerance. Thus, if a patient is able to achieve sufficient symptom management from CBD without the use of THC, they might be able to avoid or limit the effects of tolerance.

The effects of cannabis tolerance can also be mitigated through the use of a dosage schedule that incorporates a gradual increase in dosage potency. By increasing dosage gradually, patients will be able to better maintain their experienced levels of symptom relief. However, as dosage potency increases, so does the rate of tolerance, thus regardless of how carefully one schedules their treatment regimen, they will eventually experience reduced effectiveness in symptom management.

The most effective method for reducing tolerance and regaining the full symptom relief potentials of cannabis medicine, is through taking scheduled tolerance breaks (also known as ‘t-breaks’). Once a patient reaches the point where increasing their dosage to achieve greater efficacy is no longer deemed practical and/or safe, they should talk to their doctor about a tolerance break.

When a patient ceases their course of cannabis treatment for a tolerance break, research suggests that the replenishment of CB1 receptor availability can begin within the first 48 hours. Some in the medical cannabis community recommend that patients who rely on cannabis for the treatment of chronic conditions should consider taking a two day break once every 30 days, in order to limit the effects of tolerance.

For those who’s condition/symptom severity will allow for longer breaks, research indicates that after a break of two weeks, experienced effects should begin returning to normal. In four weeks, CB1 receptor function/density is observed to return to near normal.

After taking a tolerance break, patients should be aware that they might now be more susceptible to the intoxicating effects of THC than they were prior to taking this break. Patients should thus consider starting again at a lower dosage, both to avoid unwanted effects, and to gauge the possible therapeutic potentials of a lower dose.


Cessation and the Potential for Withdrawal Symptoms

Anecdotally, patients reporting that they have experienced withdrawal symptoms after stopping a course of cannabis treatment is generally uncommon, and usually involves symptoms of low to moderate severity. However, various studies on the subject have reported the rate of patients who experience some form of withdrawal symptoms as being anywhere from 35% to 75%, with a noted potential for greater symptom severity to be experienced by women.

Patients who report experiencing withdrawal symptoms typically begin experiencing symptoms between 24-72 hours following cessation. With peak symptoms being experienced after seven days. Mild symptoms can potentially persist for as many as four weeks.

The associated symptoms of cannabis withdrawal and their limited severity are sometimes likened to those commonly associated with caffeine withdrawal.

Potential symptoms can include:

  • Sudden return and/or increased severity of symptoms being managed
  • Reduced Appetite
  • Upset Stomach and/or Nausea
  • Sleep Disturbance
  • Vivid Dreams
  • Irritability
  • Mood Swings
  • Restlessness
  • Fatigue
  • Headaches
  • Loss of Focus
  • Depression
  • Dysphoria

Patients are recommended to help manage withdrawal symptoms by staying well hydrated, getting plenty of bed rest, and engaging in regular exercise to achieve a natural boost in one’s mood. Over-the-counter remedies can be useful in managing symptoms of nausea and headache. There is also some evidence to suggest that CBD can potentially help in alleviating symptoms of withdrawal.


Weaning of Dosage Prior to Cessation

In light of the evidence suggesting that there is a possibility of experiencing some form of withdrawal symptoms, it would be prudent for patients to speak with their doctor about a gradual weaning of one’s dosage prior to ending a course of treatment or beginning a tolerance break. This should be considered if frequently consuming a high THC dosage and/or an extended duration of treatment. While the gradual weaning off of cannabis medicine is far less common than immediate cessation, there is the possibility that it may help further reduce the potential for experiencing withdrawal symptoms.

For those wishing to limit the possibility of experiencing these symptoms through weaning, patients should gradually decrease the THC potency of their dosage as well as dosage frequency over the course of approximately ten days. Dosage should also be limited to the evenings while weaning, in order to best limit potential symptoms of sleep disturbance.


EXAMPLE WEANING CHART:

Original Dosage

DAY 1

DAY 2

DAY 3

DAY 4

DAY 5

DAY 6

DAY 7

DAY 8

DAY 9

DAY 10

Potency (THC)

10mg

10mg

7.5mg

7.5mg

5mg

N/A

5mg

N/A

2.5mg

N/A

2.5mg

Frequency

x 2 Morning /Evening

x 1 Evening Only

x 1

x 1

x 1

N/A

x 1

N/A

x 1

N/A

x 1


To begin your cannabis medicine journey today, book an appointment now at the Savikalpa Virtual Clinic for an online doctor consultation, or request more information from a member of our highly trained clinic staff (eclinic@savikalpa.com).

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Interested in learning more? Send us your questions (eclinic@savikalpa.com). It is our mission to educate patients in any way we can, and we would be delighted to hear from you.


Research regarding cannabis and drug tolerance:


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