Can CBD reduce the adverse effects of THC?

Purveyors of cannabis products containing cannabidiol (CBD) often claim that CBD attenuates or reduces many of the unwanted side effects of THC.

Is there any scientific evidence to support this claim? Yes, actually, but before we delve into the science,1,2,3 let’s first understand the theory.

THC and CBD are cannabinoids. They are chemical compounds found in the cannabis sativa plant. They produce biochemical effects in our bodies, in part, by interacting with cannabinoid receptors. These cannabinoids are only two of more than 100 such phytochemicals identified to date.4 When administered concurrently, THC and CBD may bind to the same cannabinoid receptor. Both are considered “partial agonists”, which means that they partially occupy receptors on the surface of cells and initiate an intracellular response within the cells.

It is thought that THC has a higher affinity for cannabinoid receptor 1 (CB1) than CBD. This basically means that THC forms a stronger bond with the CB1 receptor. THC and CBD bind to different parts of the receptor. In the presence of CBD, the conformation, or shape, of the receptor changes in a way that lowers its affinity for THC. In other words, when CBD is bound to the CB1 receptor, THC does not bind as strongly as it would in the absence of CBD. In theory, this could lead to an attenuation of the effects of THC.

THC is thought to be the primary intoxicating cannabinoid. CBD produces no intoxication or impairment. Both are “psychoactive” in that they induce changes in mental status and state.

A different theory holds that the two have opposing effects, and that any attenuation of effects produced by THC may be due to the independent and opposing effects of CBD. In fact, these effects may have nothing to do with any interaction between the two cannabinoids at the receptor.

The list of “THC effects” is long. It includes subjective and objective effects, such as intoxication, relaxation, creativity, nausea reduction, appetite stimulation, pain reduction, sedation, short-term memory impairment, muscle relaxation, euphoria, dysphoria (i.e. anxiety, sense of disease), increased heart rate, and many more. CBD has its own list of subjective and objective effects. It includes neuro-protection, anti-inflammation, anti-anxiety and immune-modulation among others.

Whether an effect is a “side-effect” or a “primary effect” depends on the therapeutic intention. If your goal is to reduce pain, then pain-reduction is the intended, primary effect and appetite stimulation, as an example, would be a potential side effect. If side effects are undesirable, they are called adverse effects.

The interaction between THC and CBD in healthy volunteers has been studied in at least four of the following studies with contradictory results. All of the studies found on this topic were conducted decades ago. Most of them could not be procured and analyzed as of this writing.

In 1974, Karniol et al. administered 30 mg of oral THC to four groups of healthy volunteers. One group received no CBD, a second group received 15 mg of CBD, a third received 30 mg, and the fourth received 60 mg. The ratio of THC to CBD in the three CBD groups was 1:0.5, 1:1 and 1:2. It was reported that CBD “diminished the subjective effects of THC”, and reduced the “component of anxiety induced by THC alone”.5

In 1975, Hollister et al. administered 20 mg of oral THC to three groups of healthy volunteers. One group also received a placebo, a second group received 40 mg of CBD, a third received 40 mg of cannabinol (CBN). No attenuation of THC effects was noted. In fact, the authors wrote that their findings offered, “…no reason to abandon the current practice of basing doses of marijuana for clinical studies solely on THC content.”

In 1976, Dalton et al. conducted two studies on the topic. In one study, 15 healthy male volunteers were given, in a double-blind manner, placebo or 150 micrograms/kg of CBD or 25 micrograms/kg of THC together with either placebo or 150 micrograms/kg of CBD in a single marijuana cigarette. According to the authors, “CBD significantly attenuated the subjective euphoria of THC. Psychomotor impairment due to THC was not significantly altered by the simultaneous administration of CBD.” This study would seem to indicate that THCs euphoric effect was attenuated, but its impairment effect was not.6

In a second study, eight healthy male volunteers were given CBD (0 or 150 micrograms/kg) by smoke inhalation 30 min before THC (0 or 25 micrograms/kg) in a second cigarette. In contrast to the simultaneous administration, “CBD pretreatment did not alter the effects of THC”.6

In Dalton’s studies, THC and CBD were delivered via inhalation, as opposed to ingestion in the prior studies. As a result, the dosages were significantly smaller. Twenty-five micrograms of THC are equal to 0.025 milligrams. Karniol et al. used a dose of THC that was 1,200 times greater per kilogram of body weight. Hollister et al. used a dose that was 800 times. This reflects the significantly higher absorption of these compounds thru the lungs as opposed to the gastrointestinal tract.

In 1982, Zuardi et al. attempted to confirm this finding in eight healthy volunteers.7 Each subject was given five different treatments in double-blinded fashion with a week in between each treatment.

The treatments were as follows:

  1. Placebo

  2. 0.5 mg/kg THC

  3. 1 mg/kg CBD

  4. 0.5 mg/kg THC + 1 mg/kg CBD

  5. 10 mg diazepam

According to the CDC, the average weight of an adult male in 2014 was 196 pounds, or 89 kilograms.8 This means that for the average American the dose of THC and CBD was 45 and 89 mg respectively, which represents a 1:2 ratio when administered concurrently. It should be pointed out that these subjects were Brazilian and that these dosages are high, especially for THC.

The THC-only group reported a much larger number of effects than the combined THC+CBD group, including difficulty concentrating, resistance to communication, depersonalization and dizziness. However, at one of four separate time points, the THC+CBD group also reported difficulty concentrating and depersonalization.

Heart rate decreased in the placebo, CBD and diazepam groups, but it increased in both groups containing THC, by the same amount. By this measure, it appears that CBD does not attenuate the increase in heart rate induced by THC.

In terms of anxiety, the placebo and CBD-only groups experienced no significant increase in anxiety, while the diazepam and THC-containing groups experienced an increase. Importantly, the CBD+THC group experienced an increase in anxiety that was roughly half of the increase that was experienced by those in the THC-only group. By this measure, it appears that CBD does attenuate the increase in anxiety induced by THC.

A series of eight opposing subjective feelings were compared two hours after taking the different treatments. Subjects were asked, for example, if they felt drowsy or alert, mentally slow or quick-witted, fuzzy or clear-minded, discontented or contented, and so on. Generally speaking, the THC-only group and the CBD-only group reported opposing effects. Two hours after taking only THC, most subjects reported feeling drowsy, incompetent, fuzzy and discontented. While most subjects taking only CBD reported feeling alert, proficient, quick-witted and clear-minded. This highlights the differing, and often opposing effects of THC and CBD. CBD does not simply attenuate THC effects. It has its own effects.

Finally, fewer subjects reported a negative effect with the THC+CBD treatment as compared to the THC treatment alone. Combined with the above, this evidence adds to the notion that CBD may attenuate some of the negative effects of THC.

The bottom line

There is some evidence in humans showing that CBD attenuates some of the negative, subjectively-reported effects of THC. These trials are small, and mostly unavailable for greater scrutiny. These effects include anxiety, mental slowness, feelings of discontent, etc. As a result, if certain therapeutic effects of THC are desired (e.g. appetite stimulation, analgesia, nausea reduction), there is a reasonable rationale for choosing a product that contains CBD in order to offset the risk of any “adverse effects” of THC. The amount of CBD, or the ratio of CBD to THC that is required, or optimal, remains to be seen.

In health,

- Dr. Jamie Corroon, ND, MPH

Despite the favorable safety profile, dosing and administration of cannabinoids is complicated. The process should be highly individualized, and is best supervised by a trained health care professional. For more information, please consider booking a consultation (telephone or in-person) with Dr. Jamie Corroon, ND, MPH.

References:

1. Hollister LE, Gillespie H. Interactions in man of delta-9-tetrahydrocannabinol. II. Cannabinol and cannabidiol. Clin Pharmacol Ther. 1975;18(1):80-83. http://www.ncbi.nlm.nih.gov/pubmed/1097148. Accessed July 3, 2017.

2. Karniol IG, Shirakawa I, Takahashi RN, Knobel E, Musty RE. Effects of delta9-tetrahydrocannabinol and cannabinol in man. Pharmacology. 1975;13(6):502-512. http://www.ncbi.nlm.nih.gov/pubmed/1221432. Accessed July 16, 2017.

3. Dalton WS, Martz R, Lemberger L, Rodda BE, Forney RB. Influence of cannabidiol on delta-9-tetrahydrocannabinol effects. Clin Pharmacol Ther. 1976;19(3):300-309. doi:10.1002/cpt1976193300.

4. Roy Upton, RH AHP. Cannabis Inflorescence, Cannabis Spp. Standards of Identity, Analysis, and Quality Control.; 2014.

5. Karniol IG, Shirakawa I, Kasinski N, Pfeferman A, Carlini EA. Cannabidiol interferes with the effects of delta 9 - tetrahydrocannabinol in man. Eur J Pharmacol. 1974;28(1):172-177. http://www.ncbi.nlm.nih.gov/pubmed/4609777. Accessed July 3, 2017.

6. Dalton WS, Martz R, Lemberger L, Rodda BE, Forney RB. Influence of cannabidiol on delta-9-tetrahydrocannabinol effects. Clin Pharmacol Ther. 1976;19(3):300-309. http://www.ncbi.nlm.nih.gov/pubmed/770048. Accessed July 3, 2017.

7. Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 1982;76(3):245-250. http://www.ncbi.nlm.nih.gov/pubmed/6285406. Accessed May 5, 2017.

8. CDC. FastStats - Body Measurements. https://www.cdc.gov/nchs/fastats/body-measurements.htm. Accessed July 16, 2017.

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