Cannabis Research Analysis

Frank, Kurtis; Patel, Kamal; Lopez, Gregory; Willis, Bill

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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.

Research analysis led by Kamal Patel and reviewed by the Examine team.
Last Updated: Mar 8, 2021

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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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 [show legend]
	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

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
Symptoms of Multiple Sclerosis	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.
Heart Rate	Notable	Very High See all 12 studies	Smoking cannabis generally increases heart rate when taken acutely.
Anxiety	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.
Blood Pressure	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.
Cerebral Blood Flow	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.
Motor Control	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).
Neuropathic Pain (In general)	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.
Pain	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.
Sleep Quality	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.
Tourette Syndrome	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.
ADHD	-	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.
Attention	-	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.
Depression	-	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.
Fatigue	-	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.
Schizophrenia	-	- 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.
Relaxation	Notable	- See study	The dose and time which confer psychoactive effects are associated with reported of relaxation to a larger degree than control.
Aerobic Exercise	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.
Cancer Pain (Various)	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.
Dizziness	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.
Driving Control	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.
Driving Speed	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.
Ghrelin	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.
Incontinence	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.
Leptin	Minor	Very High See 2 studies	An increase in leptin has once been noted with usage of cannabis.
Lung Function	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.
Opioid Use	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.
Peptide YY (PYY)	Minor	- See study	A decrease in serum peptide YY has been noted with cannabis usage, thought to be tied into its interactions with appetite.
Reaction Time	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.
Symptoms of Orthostatic Hypotension	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)
Working Memory	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.
Blood Flow	-	- 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.
Body Temperature	-	- See study	No significant influence on body temperature.
Cognition	-	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.
Driving Caution	-	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.
Insulin	-	- See study	Short term cannabis usage does not influence circulating insulin concentrations.
Irritability	-	Very High See 2 studies	Irritability as a side effect of multiple sclerosis does not appear to be significantly affected by cannabis therapy.
Memory	-	Very High See 2 studies	Overall memory formation does not appear to be significantly affected by usage of cannabis.
Power Output	-	- See study	Acute inhalation of cannabis failed to modify grip strength when tested compared to control.
Angina	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.
Balance	Notable	Very High See 2 studies	In two studies, there was an improvement, in those with multiple sclerosis and healthy participants.
Impulsivity	Notable	- See study	One study found a notable reduction in ADHD from continual use of an oromucosal spray. More research is needed.
Intraocular Pressure	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.
Metabolic Rate	Notable	- See study	Seems to be increased for at least an hour, maybe two, after smoking. More research is needed.
Nausea	Notable	- See study	One study found a reduction in chemotherapy-induced nausea from oral THC/CBD capsules.
Pulse Rate	Notable	- See study	Acute smoking led to a notable increase for roughly 3 hours.
Symptoms of Burning Mouth Syndrome	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.
Aggression	Minor	- See study	One study found a reduction in heavy cannabis and alcohol users. More research is needed.
Appetite	Minor	High See all 3 studies	Appetite was increased in two studies on normal participants, but not one in cancer-related anorexia-cachexia syndrome.
Confusion	Minor	- See study	Acute smoking appeared to increase confusion in one study.
Crohn’s Disease	Minor	- See study	One study foiund an improvement, though it wasn't statistically significant.
Food Intake	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.
Glucagon-like peptide 1 (GLP-1)	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.
Hand-Eye Coordination	Minor	- See study	One study found a reduction after acute oral dosing.
Luteinizing Hormone	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.
Lymphocyte Count	Minor	- See study	One study found an increase after 21 days of smoking in HIV-1 patients. More research is needed.
Mood	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.
Motor Speed	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.
Natural Killer Cell Activity	Minor	- See study	One study found an increase in HIV-1 patients when smoked for 3 weeks.
Pain From Wounds	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.
Perceived Fullness	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.
Prolactin	Minor	- See study	Somewhat of a decrease was found when smoking cannabis acutely in one study.
Sleep Latency	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.
Social Functioning	Minor	- See study	A reduction in willingness to talk during social time was found in one study.
Subjective Well-Being	Minor	- See study	Improvement was secondary to an improvement in fibromyalgia. (This outcome is incomplete and doesn't include the results from various studies)
Symptoms of Fibromyalgia	Minor	Very High See 2 studies	Two studies have found positive effects of acute and chronic use on pain. More research is needed.
Symptoms of Myotonia	Minor	- See study	One uncontrolled study found some improvements from THC/CBD oil. More research is needed.
Symptoms of Rheumatoid Arthritis	Minor	- See study	An improvement in pain but not stiffness was found with the use of oromucosal spray over the course of 3 weeks.
Symptoms of Sickle Cell Disease	Minor	- See study	Vaporized cannabis appeared to reduce pain in general, but the difference wasn't statistically significant. More research is needed.
Testosterone	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.
Verbal Memory	Minor	- See study	One study found a reduction when taken acutely.
Vomiting	Minor	- See study	A reduction was found in chemotherapy patients in one study.
Walking	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.
Weight Gain	Minor	- See study	An increase was observed in cancer-related cachexia and anorexia. in one uncontrolled study. More research is needed.
B-Cell Count	-	- See study	No apparent effect in HIV-1 patients.
Breathing Rate	-	- See study	Breathing rate does not appear to be inherently altered with usage of cannabis.
C-Reactive Protein (CRP)	-	- See study	No apparent effect of smoking cannabis cigarettes over 8 weeks in one study.
CD4 Lymphocytes	-	- See study	No apparent effect in HIV-1 patients in one study.
CD8 Lymphocytes	-	- See study	No apparent effect in HIV-1 patients in one study.
Cortisol	-	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.
Hematocrit	-	- See study	Possibly a small reduction in one study, but with a lack of statistical significance.
Hemoglobin	-	- See study	No apparent effect over 8 weeks in one study.
Natural Killer Cell Content	-	- See study	No apparent effect in HIV-1 patients when smoked for 3 weeks.
Quality of Life	-	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)
Sleep Duration	-	- See study	No apparent effect in one study in multiple sclerosis.
Symptoms of Diabetic Neuropathy	-	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.
Symptoms of Parkinson's Disease	-	- See study	No apparent benefit in one study.
Tobacco Consumption	-	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.
VO₂ Max	-	- See study	Despite a reduction in endurance (cycling until voluntary failure) the measured VO2 max between groups did not differ.
Visual Acuity	-	- See study	During treatment of glaucoma with THC, visual acuity did not appear to be hindered.
White Blood Cell Count	-	- 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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Study Deep Dives

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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.

Read full answer to "The science behind munchies: cannabis and your appetite"

Things to Note

Primary Function:

Mood

Other Functions:

Cognitive Function and Brain Health

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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Cannabis

Summary of Cannabis

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

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How to Take

Recommended dosage, active amounts, other details

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Human Effect Matrix

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Studies Excluded from Consideration

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Study Deep Dives

Frequently Asked Questions and Articles on Cannabis

Things to Note

Primary Function:

Other Functions:

Also Known As

Do Not Confuse With

Goes Well With

Caution Notice

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Research Breakdown on Cannabis

1.1Origin and Composition

1.2Physicochemical Properties

2.1Absorption

2.2Transportation in Serum

2.3Peripheral Distribution

2.4Metabolism

2.5Elimination

2.6Phase I Enzyme Interactions

3.1Vaporizing

3.2Oromucosal spray (Nabiximols, Sativex)

3.3PTL401

3.4Namisol

3.5Blunts

3.6Dabbing (Butane Hash Oil)

4.1Cannabinoid Receptors

4.2Other Receptors

4.3Ion Channels

4.415-LOX

5.1Adenosinergic Neurotransmission

5.2Adrenergic Neurotransmission

5.3Agmatinergic Neurotransmission

5.4Cannabidergic Neurotransmission

5.5Cholinergic Neurotransmission

5.6Dopaminergic Neurotransmission

5.7GABAergic Neurotransmission

5.8Glutaminergic Neurotransmission

5.9Glycinergic Neurotransmission

5.10Opioidergic Neurotransmission

5.11Serotonergic Neurotransmission

5.12Neurogenesis

5.13Neuroinflammation

5.14Headaches and Blood Flow

5.15Analgesia

5.16Appetite and Food Intake

5.17Attention and Focus

5.18Sedation and Sleep

5.19Epilepsy and Convulsions

5.20Anxiety and Stress

5.21Depression

5.22Memory and Learning

6.1Cardiac Tissue

6.2Atherosclerosis

6.3Blood Pressure

6.4Platelets and Viscosity

6.5Triglycerides

6.6Cholesterol

7.1Insulin

7.2Insulin Sensitivity

7.3Blood Glucose

7.4Glycogen

7.5Glycation

7.6Type I Diabetes