What Is the Cannabis Therapeutic Window?
Last updated on Oct 7, 2024
Created on Apr 2, 2023
Article written by
Emma Stone
Like all medicines, medical marijuana has a sweet spot that starts at its lowest effective dose and spans to the dose that it begins to produce unwanted side effects. This range is known as the cannabis therapeutic window, and it can vary among cannabis users.
Those new to medicinal cannabis often discover that their therapeutic window is narrow, whereas seasoned users tend to have a larger window due to higher tolerance levels.
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What Is a Therapeutic Window?
A therapeutic window, also known as a therapeutic index (TI) or a therapeutic ratio, refers to the dosing range between the onset of a drug’s therapeutic effects and the point at which adverse effects begin. In general, the therapeutic window of a drug is determined by measuring plasma concentrations during human clinical trials and identifying the specific range of doses at which a medicine appears to be effective for most participants without unacceptable adverse effects. The purpose of a therapeutic window is to provide an adequate safety margin for individuals prescribed the drug or medicine.
Therapeutic windows can vary across different drugs. Some have a larger therapeutic window, while others have a narrow one. The larger the therapeutic window, the safer the drug is. On the other hand, drugs with a narrower therapeutic index have a “steep concentration-response relationship.” In other words, there is only a slim margin between the medicine delivering benefits and posing a risk to the consumer.
The Therapeutic Window of Cannabis
Some experts believe that medical cannabis, specifically THC present in cannabis, has a relatively narrow therapeutic window. CBD, however, has a larger therapeutic window.
Many individuals who use medical marijuana turn to the plant for issues as diverse as neuropathic pain, chronic pain, or anxiety. However, new patients can sometimes experience difficulty finding a dose that offers relief without triggering unpleasant effects.
In high doses, THC can cause paranoia, anxiety, panic, dizziness, dry mouth, or coordination and motor control difficulties. This narrow therapeutic window means that some patients who try medical cannabis discontinue use because they have trouble experiencing therapeutic benefits without the unpleasant effects of THC, or they turn to products with even ratios of THC to CBD.
However, it’s important to differentiate medical cannabis from other drugs with narrow therapeutic windows. Although medical cannabis may cause unpleasant adverse effects at high concentrations, it won’t lead to toxicity and death (like it would with fentanyl or morphine). To date, the risk of death due to cannabis toxicity is negligible.
A number of clinical studies have specifically explored the medical marijuana therapeutic window. In a comprehensive review of the effects of medical cannabis and cannabinoids on multiple sclerosis, the authors found that THC and THC:CBD products could help reduce muscle spasms and provide pain relief from neuropathic pain. However, the narrow therapeutic index of THC products limited their use.
In another clinical review of medical marijuana as a treatment for pain, the authors found that the usefulness of medical cannabis as a treatment for acute pain relief was limited by the poorly understood therapeutic window and dose-dependent side effects.
Overall, these clinical trials (among many others) suggest that there is still much for us to learn about the cannabis therapeutic window. Cannabis is categorized as a Schedule I drug in the United States by the DEA, which has rendered clinical trials on the plant (such as a better understanding of its therapeutic window) extremely challenging.
Factors That Affect the Cannabis Therapeutic Window
There is a range of factors that can influence the cannabis therapeutic window. These are caused by differences among individuals and include genetics, metabolism, biological sex, and more.
Genetics
Certain individuals have an increased genetic sensitivity to the effects of cannabis. This genetic sensitivity can mean that a very low dose may produce strong effects that would not impact the average person.
Metabolism
Studies indicate that certain individuals may metabolize THC more quickly than others. Differences in how the cannabinoid is metabolized may be due to biological or genetic variation.
Biological Sex
Studies suggest that the cannabis therapeutic window may vary between men and women. For example, experts theorize that women may experience weaker THC effects than men because women have a higher percentage of body fat, and delta 9-THC is retained by fat cells. This suggests that men are more sensitive to the subjective effects of THC.
However, women show higher expressions of CB1 receptors than men, and many other studies show that women report both positive and negative effects. More research is needed to determine differences in cannabinoid receptor expression in both males and females, taking age into account as well.
Drug-drug Interactions
The therapeutic window of cannabis can also be affected by interactions with other drugs or medicines. It’s important to be aware that marijuana use can cause potential drug-drug interactions with many common medications. For example, additive effects can occur when weed is combined with central nervous system depressants such as alcohol, opioids, and anticholinergics (e.g., dicyclomine).
General Health
Your health and well-being can also impact how your body responds to cannabis. For example, if medicinal marijuana is used for multiple sclerosis, which is characterized by chronic pain, the therapeutic window may change if symptoms worsen. Similarly, if an individual uses weed to treat a condition that improves over time, the therapeutic window for that individual may also shift.
Weight
An individual’s weight may also impact how the body metabolizes the plant. The cannabinoids in cannabis are fat-soluble, meaning they can bind to fat molecules and linger in the body longer. People with high body fat concentrations may metabolize marijuana more slowly, while those with low concentrations may experience a more rapid onset of effects.
Tolerance
Finally, the development of tolerance plays a major role in how the body responds to cannabis. Tolerance means that an individual experiences a diminished response to a drug when used repeatedly, and the body adapts to its continued presence. Cannabis tolerance can be developed with regular marijuana use in as few as seven days.
Tolerance is a double-edged sword as it means that weed’s adverse effects diminish; however, the intended therapeutic effects can also wane, requiring higher doses. Chronic cannabis users or individuals who take cannabis for health conditions, such as chronic neuropathic pain, occasionally have to engage in practices to reset tolerance, such as “T breaks.”
In general, it’s important to remember that the status of an individual is never static but always changing. Weight changes, dietary changes, the onset or resolution of an illness, and fluctuations in cannabis use can all impact an individual’s cannabis therapeutic window.
How to Determine Your Cannabis Therapeutic Window
An exact cannabis therapeutic window or index hasn’t yet been established. Cannabis therapeutic experts often point out that finding one’s cannabis therapeutic window is a personal journey, and it’s advisable to “start low and go slow.” When determining the dose that’s right for you, it’s helpful to think about your intended goals and personal circumstances. For example, your dosing needs may be different if you’re consuming cannabis for its analgesic effects (pain-relieving effects) versus consuming it to ward off weight loss during chemotherapy.
In general, a sound rule of thumb is to start with a very low dose (2 mg-2.5 mg), slowly titrate (adjust the dose), and observe or record the effects with each change. When you start to experience the intended therapeutic effects without any unwanted side effects, you’ve found the lower end of your therapeutic window. When you begin to experience adverse events with increased doses, that represents the upper limit of your therapeutic window.
Microdosing represents a cautious approach that allows you to start with very low doses that deliver mild therapeutic benefits without intoxicating effects. The usual starting dose for THC is 2.5 mg. The dose can then be increased in 2.5 mg increments until the desired therapeutic effects are experienced.
The oral administration of cannabis tinctures or edibles represents an easy delivery method for precise dosing because the packaging contains the exact amount of cannabinoid content in relation to the bottle’s volume. Microdosing raw cannabis flower can be a little more complicated, but it can be achieved. It’s also somewhat easier to observe the effects of cannabis after smoking or vaping, as the onset can occur in as few as ten minutes.
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The Bottom Line
The cannabis therapeutic window refers to the dosing range between the onset of the plant’s therapeutic effects and the point at which adverse events begin. The THC in cannabis is believed to have a relatively narrow therapeutic window, so it’s vital to dose slowly and mindfully as you inch your way toward your desired therapeutic effects. It’s also essential to be aware that diverse factors, such as personal tolerance levels, health, and weight, may affect your personal therapeutic window.
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