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Cannabis

Cannabis is the common name and genus for a few plants used around the world due to their psychoactive properties. Its major component, known as THC, possesses acute benefits but is subject to rapid tolerance. Additionally, nonpsychoactive components like CBD may have chronic benefits. While therapeutic, particularly for pain relief, the plant is not a panacea.

Our evidence-based analysis on cannabis features 814 unique references to scientific papers.

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Summary of Cannabis

Primary information, health benefits, side effects, usage, and other important details

Cannabis is the common name for a few plants in the cannabis genus, including sativa, indica, and ruderalis. It is primarily used for its psychoactive properties around the world. Cannabis has also been traditionally used to treat inflammatory disorders and is increasingly being used in modern medicine.

Cannabis' primary active chemical, Δ9THC, or delta-9 tetrahydrocannabinol, acts on the cannabinergic system in the body, which is actually named cannabis after the plant. This system is regulated by two receptors, called cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2). CB1 is responsible for most of the psychoactive effects of cannabis, and CB2 is responsible for many of the long-term benefits cannabis may provide for inflammation and related diseases.

THC and CBD appear to be notable analgesics and can reduce pain in a variety of health conditions. Pain in multiple sclerosis and neuropathic pain, in general, have the best evidence for benefits, and they also appear to be useful in cancer, fibromyalgia, rheumatoid arthritis, and pain from wounds. However, more research on those is needed. There is great interest in using cannabis to reduce opioid use, and while some evidence supports this, more research is needed to determine where it may be most effective. In instances of severe pain, the reduction in pain may not be enough to reduce opioid use.

Inhaling cannabis smoke increases diastolic blood pressure and heart rate, though this change is temporary. However, many case studies note cannabis usage 30 – 60 minutes before heart attacks, so it's possible that this acute effect could be dangerous for those at high risk. Heart attacks can occur when people with an elevated risk for heart disease push their blood pressure and heart rate to dangerous levels. It may also interact with some pharmaceuticals, which could result in elevated blood pressure and a heart attack. Smoking cannabis has also been associated with bronchitis.

Cannabis usage over a long period of time can cause tolerance and subsequently withdrawal. Cannabis withdrawal is recognized by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). On a molecular level, cannabis tolerance occurs when the CB1 receptor is overstimulated and internalized, meaning absorbed by the cell. The CB1 receptor and the N-methyl-D-aspartate receptor (NMDA) receptor are linked when it comes to cannabis, so when CB1 signaling is inhibited, NMDA signaling is also hampered. This may cause cannabis to be less effective for treating epilepsy and schizophrenia, though it also reduces the memory loss associated with cannabis use. Tolerance does not significantly affect the CB2 receptor, so cannabis may be effective for inflammatory disorders over a longer period of time.

Note:

Originally, this page included various studies on isolated THC. We have decided to transition the Human Effect Matrix of this page to one that exclusively includes studies on combinations of THC and CBD, either in the form of whole cannabis leaf, cannabis oil, or pharmaceutical combinations of THC and CBD. We have a dedicated CBD page and hope to release a dedicated THC page in the not-too-distant future.

In one sense, this should provide us a better way to understand the expected effects of different products. On the other hand, because a large amount of clinical research is in isolated and synthetic THC, this page by itself is insufficient, in a sense. Various painful conditions that respond to isolated THC could also benefit the same dose of THC from whole cannabis or a THC/CBD product, as the addition of CBD or the other parts of cannabis will be unlikely to counteract those effects; if anything CBD appears to be a notable analgesic in its own right. So when you're using this page, know that there's a good chance that there is more research on isolated THC or CBD for various outcomes (especially chemotherapy side-effects).

This page is also incomplete because we have omitted some research that we didn't find to be particularly useful for this page. This included a vast literature on the psychological and cognitive effects of cannabis, largely when taken acutely. It also included various studies on health conditions where there were very few applicable studies, though these will be added next update.

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How to Take

Recommended dosage, active amounts, other details

Cannabis is usually inhaled to experience its psychoactive effects but can also be taken orally, sublingually (placed and held under the tongue), or via suppository. The route of consumption will dictate how quickly its effects will be felt with inhalation and suppository acting faster than sublingual or oral consumption.

The benefits and side-effects related to cannabis consumption will typically occur at doses large enough to cause a mild to moderate high. The most common dose range used in clinical trials is 2–5 mg per day (although this dose is typically concentrated THC).

Most side-effects of cannabis use are associated with frequency, not dosage. Using cannabis more than once a week might result in tolerance. Some people may need to restrict their usage to twice a month to avoid developing a tolerance.

Do not increase cannabis doses to overcome tolerance unless directed to do so by a medical professional.

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Human Effect Matrix

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The Human Effect Matrix summarizes human studies to tell you what effects Cannabis has on your body, how much evidence there is, and how strong these effects are.

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Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-a Minor Very High See all 20 studies
Oral cannabis extract appears to modestly reduce pain and bladder dysfunction, while Nabiximols doesn't appear to be effective. For spasticity symptoms, neither of these products shows a clinically significant effect on an objective rating scale, though participants report modest subjective improvements. The effects of cannabis on cognitive symptoms are unclear.
grade-b Notable Very High See all 12 studies
Smoking cannabis generally increases heart rate when taken acutely.
grade-b Minor Very High See 2 studies
Note: We have not specifically reviewed all of the literature on this subject and are referring to the results of a meta-analysis that included isolated THC. In that case, evidence suggests a modest, statistically significant reduction. However, study quality appears to be low, and most studies aren't in anxiety disorders but recorded anxiety symptoms in other conditions.
grade-b
Minor
- See all 8 studies
Increases, decreases, and no effect have all been noted. One possibility is that in a new user, it will increase blood pressure and this is subject to tolerance. Heavy users may not experience this acute increase anymore and may instead have a decrease in diastolic blood pressure. However, the evidence for this isn't entirely consistent, and much more research is needed.
grade-b
Minor
- See all 3 studies
Both increases and decreases seem to have been reported over the whole brain, and it seems that in people who do not experience orthostatic hypotension from cannabis it is generally an increase; blood flow to the ACC in particular is increased following THC, but this becomes a decrease during tolerance.
grade-b Minor Very High See all 4 studies
Acute usage can reduce motor control and fine coordination, but this appears to be an effect that can be subject to tolerance (with tolerant users not seeing any difference following usage of cannabis).
grade-b Minor Very High See all 18 studies
There's a modest but rather reliable reduction in general neuropathic and multiple-sclerosis-related pain when taking cannabis. It should be noted that most cannabis (rather than isolated THC) studies are using an oromucosal spray with THC and CBD, so this may not translate to other forms, and much of this research is industry-sponsored. What research we have on smoking and vaporizing cannabis does suggest that it effectively relieves pain.
grade-b Minor Very High See all 6 studies
There appears to be a reduction in pain associated with the dose of cannabis which confers psychoactive effects.
grade-b Minor Very High See all 10 studies
Secondary to some benefits to physical symptoms in the treatment of multiple sclerosis, cancer, and general neuropathic pain, sleep quality is generally improved by cannabis. It's not clear what the effects in other scenarios are, however.
grade-b Minor - See study
Note: we have not reviewed the individual studies and are merely reporting on a meta-analysis. A small amount of research suggests a possible improvement but the results aren't statistically significant.
grade-b - Very High See 2 studies
There is currently very little evidence. It is possible that there is some effect on some symptoms, but much more research is needed.
grade-b - Very High See all 6 studies
One study found a nonsignificant increase in ADHD from a combination of THC and CBD, while another found a reduction for healthy participants when taking CBD and THC. The rest didn't find an effect.
grade-b - Very High See all 7 studies
Depression as a symptom of multiple sclerosis does not appear to be significantly affected by cannabis therapy. One study found higher rating of depression on a mood scale when taking CBD and THC acutely, but this was in healthy participants and hasn't been replicated.
grade-b - Very High See all 7 studies
Mixed evidence in regards to physical and mental fatigue in the usage of cannabis for multiple sclerosis, with more studies suggesting the benefits are not statistically significant. There may be a bit of an acute energizing effect for healthy participants but more research is needed. One study also found a reduction secondary to improvement in fibromyalgia.
grade-b - - See study
Note: we have not reviewed the individual studies ourselves and are simply reporting on this meta-analysis currently. A small amount of research is currently inconclusive for positive and negative symptoms.
grade-c Notable - See study
The dose and time which confer psychoactive effects are associated with reported of relaxation to a larger degree than control.
grade-c Minor Very High See 2 studies
It seems that submaximal (light) aerobic exercise performance is not influenced much, but when aerobic exercise is carried to fatigue cannabis usage seems to be associated with less endurance relative to control.
grade-c Minor Very High See all 5 studies
Appears to be effective for reducing pain in various cancers. All included studies used oromucosal THC and CBD spray and were funded by industry, so much research is needed before greater confidence in the results can be had.
grade-c Minor - See study
Dizziness has been reported as a side-effect specifically in users who experience orthostatic hypotension from cannabis; no major influence on dizziness otherwise.
grade-c Minor High See all 7 studies
In general, there seemed to be a worsening of vehicle control while driving when taking cannabis, and this can happen for regular cannabis users or infrequent users.
grade-c Minor Low See all 4 studies
While not a consistent effect, there was some evidence of participants reducing driving speed when distracted or simply undergoing a demanding driving simulation,. More research is needed to understand the contexts that may lead to different driving behaviors.
grade-c Minor Very High See all 3 studies
An increase in ghrelin has been noted with cannabis usage, likely playing a role in the increase in appetite.
grade-c Minor Very High See 2 studies
In a secondary data analysis on subjects with multiple sclerosis, it seems the side effect of incontinence may be reduced with cannabis usage.
grade-c Minor Very High See 2 studies
An increase in leptin has once been noted with usage of cannabis.
grade-c Minor Very High See all 3 studies
While smoking per se is seen as negative, infusions of THC enhance lung function and acute usage of cannabis as joints seem to confer more benefit to lung function than drawbacks.
grade-c Minor Moderate See all 6 studies
The evidence is mixed and some studies have found a reduction when using oromucosal THC/CBD spray, as well as smoking cannabis leaf. The one large negative study was in particularly severe advanced cancer pain and so this may not have been a context where patients would voluntarily reduce opioid use. It should be noted that the research is largely funded by industry.
grade-c Minor - See study
A decrease in serum peptide YY has been noted with cannabis usage, thought to be tied into its interactions with appetite.
grade-c Minor Very High See 2 studies
A reduction in reaction time has been noted in acute users of cannabis relative to control. While not directly tested, it is thought that this is attenuated during tolerance.
grade-c Minor Very High See all 3 studies
While not affecting all users, some new users may experience symptoms of orthostatic hypotension associated with a global decrease of blood flow to the brain (rather than the expected increase)
grade-c Minor Moderate See all 4 studies
Acute working memory is decreased in new users of cannabis while under the influence, but during cannabis tolerance this hindering effect does not appear to persist.
grade-c - - See study
Despite alterations in cardiac output and diastolic blood pressure, acute usage of cannabis does not appear to influence the flow of blood relative to control.
grade-c - - See study
No significant influence on body temperature.
grade-c - Very High See all 6 studies
When used during multiple sclerosis, a general battery of cognitive function does not appear to be greatly influenced (positive or negative) with cannabis therapy.
grade-c - Moderate See all 5 studies
In some instances, the participants exhibited greater caution when driving, in others caution was reduced, though there were various null findings as well. More research is needed before we can understand the effect of different contexts.
grade-c - - See study
Short term cannabis usage does not influence circulating insulin concentrations.
grade-c - Very High See 2 studies
Irritability as a side effect of multiple sclerosis does not appear to be significantly affected by cannabis therapy.
grade-c - Very High See 2 studies
Overall memory formation does not appear to be significantly affected by usage of cannabis.
grade-c - - See study
Acute inhalation of cannabis failed to modify grip strength when tested compared to control.
grade-d Notable - See study
In one study, participants with already-present stable exertional angina saw a shorter time until experiencing angina during exercise. More research is needed.
grade-d Notable Very High See 2 studies
In two studies, there was an improvement, in those with multiple sclerosis and healthy participants.
grade-d Notable - See study
One study found a notable reduction in ADHD from continual use of an oromucosal spray. More research is needed.
grade-d Notable Very High See all 3 studies
Inhalation of cannabis is able to reduce intraocular blood pressure quite significantly, leading to it being useful in instances of glaucoma.
grade-d Notable - See study
Seems to be increased for at least an hour, maybe two, after smoking. More research is needed.
grade-d Notable - See study
One study found a reduction in chemotherapy-induced nausea from oral THC/CBD capsules.
grade-d Notable - See study
Acute smoking led to a notable increase for roughly 3 hours.
grade-d Notable - See study
A notable reduction in one trial from 1 g of cannabis diluted in 10 g of olive oil. The trial wasn't controlled, however.
grade-d Minor - See study
One study found a reduction in heavy cannabis and alcohol users. More research is needed.
grade-d Minor High See all 3 studies
Appetite was increased in two studies on normal participants, but not one in cancer-related anorexia-cachexia syndrome.
grade-d Minor - See study
Acute smoking appeared to increase confusion in one study.
grade-d Minor High See all 3 studies
Mixed and preliminary evidence, but more research supports an increase in food consumption after using cannabis. One study was acute, and the other was over the course of weeks, but in a residential laboratory.
grade-d
Minor
- See study
One study found a reduction from oral cannabis but not smoking or vaporizing. This is likely due to unique effects in the gastrointestinal tract.
grade-d Minor - See study
One study found a reduction after acute oral dosing.
grade-d Minor Moderate See 2 studies
Mixed evidence. One study found a reduction after short-term smoking, while another study didn't find an effect of acute use. The long-term implications are unknown.
grade-d Minor - See study
One study found an increase after 21 days of smoking in HIV-1 patients. More research is needed.
grade-d Minor Moderate See all 4 studies
Overall more of an increase when taken acutely, or secondary to seeing improvements in some other condition. One study noted a worsening of mood from acute use of THC/CBD, and more research is needed.
grade-d Minor Very High See 2 studies
One study found a reduction when taken acutely, which is unsurprising. Another study found a reduction in multiple sclerosis when taken chronically, which is more concerning, and more research is needed.
grade-d Minor - See study
One study found an increase in HIV-1 patients when smoked for 3 weeks.
grade-d Minor - See study
One study found a dose-dependent effect for reducing postoperative pain, with 10 and 15 mg being more long-lasting than 5 mg.
grade-d
Minor
- See study
Ratings of fullness were higher after taking high-CBD cannabis compared to high-THC cannabis, but neither were significantly different from the placebo group.
grade-d Minor - See study
Somewhat of a decrease was found when smoking cannabis acutely in one study.
grade-d Minor Moderate See 2 studies
One study found a reduction in sleep latency, likely secondary to a reduction in neuropathic pain. Another study didn't find an effect in young adults, though 5 mg of THC and CBD may have had a modest effect.
grade-d Minor - See study
A reduction in willingness to talk during social time was found in one study.
grade-d Minor - See study
Improvement was secondary to an improvement in fibromyalgia. (This outcome is incomplete and doesn't include the results from various studies)
grade-d Minor - See study
One study foiund an improvement, though it wasn't statistically significant.
grade-d Minor Very High See 2 studies
Two studies have found positive effects of acute and chronic use on pain. More research is needed.
grade-d Minor - See study
One uncontrolled study found some improvements from THC/CBD oil. More research is needed.
grade-d Minor - See study
An improvement in pain but not stiffness was found with the use of oromucosal spray over the course of 3 weeks.
grade-d Minor - See study
Vaporized cannabis appeared to reduce pain in general, but the difference wasn't statistically significant. More research is needed.
grade-d Minor - See study
An increase in total body water has been noted in hospitalized subjects alongside weight gain; practical relevance for a free roaming user not known.
grade-d Minor - See study
One study found a reduction when taken acutely.
grade-d Minor - See study
A reduction was found in chemotherapy patients in one study.
grade-d Minor Moderate See 2 studies
Mixed evidence. One study found a benefit in multiple sclerosis, and another didn't. The negative study was longer and used oromucosal spray while the positive study was shorter and used cannabis cigarettes.
grade-d Minor - See study
An increase was observed in cancer-related cachexia and anorexia. in one uncontrolled study. More research is needed.
grade-d - - See study
No apparent effect in HIV-1 patients.
grade-d - - See study
Breathing rate does not appear to be inherently altered with usage of cannabis.
grade-d - - See study
No apparent effect of smoking cannabis cigarettes over 8 weeks in one study.
grade-d - - See study
No apparent effect in HIV-1 patients in one study.
grade-d - - See study
No apparent effect in HIV-1 patients in one study.
grade-d - Low See all 3 studies
Mixed evidence. One study found a reduction in response to stimuli to provoke aggression, one study found an increase under normal conditions, and another study found no effect under normal conditions.
grade-d - - See study
Possibly a small reduction in one study, but with a lack of statistical significance.
grade-d - - See study
No apparent effect over 8 weeks in one study.
grade-d - - See study
No apparent effect in HIV-1 patients when smoked for 3 weeks.
grade-d - Very High See 2 studies
No apparent effect in two studies on cancer-related cachexia and anorexia. (This outcome is incomplete and doesn't take all studies into account)
grade-d - - See study
No apparent effect in one study in multiple sclerosis.
grade-d - Moderate See 2 studies
Mixed evidence. One study found a benefit from smoking a high dose (7% THC, but not 4 or 1) acutely but a 2-week study with oromucosal spray didn't find an improvement.
grade-d - - See study
No apparent benefit in one study.
grade-d - Low See all 3 studies
One study found modestly less tobacco smoking after smoking cannabis, which they attributed to a delay in time until smoking the first tobacco cigarette. Other studies didn't find a notable effect acutely or chronically.
grade-d - - See study
Despite a reduction in endurance (cycling until voluntary failure) the measured VO2 max between groups did not differ.
grade-d - - See study
During treatment of glaucoma with THC, visual acuity did not appear to be hindered.
grade-d - - See study
No apparent effect in one study.

Studies Excluded from Consideration

Note: Studies included in the HEM include all methods of administration except injections. Some benefits may be unique to oral supplementation (brownies) or inhalation (joints), and the commentary section will elucidate these differences if present

  • Used injections exclusively[1][2]

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Frequently Asked Questions and Articles on Cannabis

The science behind munchies: cannabis and your appetite
Tetrahydrocannabinol (THC), a cannabinoid in cannabis, can bind the cannabinoid receptor type 1 (CB1) and thus promote overeating and weight gain. This effect, detrimental to most people, can prove beneficial under certain medical conditions, such as cancer and HIV-associated wasting syndrome.

Things to Note

Primary Function:

Also Known As

Weed, Medical Marijuana, Marihuana, dope, ganja, hashish, Dronabinol (medical THC), Cannabis indica, Cannabis sativa, Marijuana

Do Not Confuse With

Hemp Protein (same plant, but this term tends to refer to a food product without THC)

Goes Well With

  • COX2 inhibitors (may reduce memory deficits associated with cannabis)

Caution Notice

Cannabis has a variable legal status depending on region, and may be illegal (to varying degrees) in your region if not for medicinal purposes.

Known drug and enzyme interactions.

  • Cannabis is highly psychoactive via both an oral and inhaled route

  • Cannabis can acutely reduce motor control and attention (and should not be inhaled prior to operating heavy machinery)

  • Cannabis is known to interact with many enzymes of drug metabolism of which include CYP3A4 and CYP2C19; see pharmacokinetic section for more information

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