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How Does CBD Interact with Our Body and Brain?
Let’s put this into perspective: CBD should be thought of as “non-intoxicating,” rather than “non-psychotropic.” Accumulated evidence demonstrates that, to a limited extent, CBD may positively influence:
Larger, randomized controlled clinical studies are required to further determine and characterize these effects. Yet, the information collected so far is promising.
In our brain and spinal cord, CB1 receptors are found in abundance. Admittedly, CBD does not directly act on them. Instead, it changes the effect that direct agents, like THC, have on CB (cannabinoid) receptors.
Further pre-clinical biochemical investigation shows that CBD’s health potential stems from its interaction with various receptors like 5HT1A (serotonin) and BDNF. This may explain some anti-anxiety and anti-depressant effects.
The observed antipsychotic effects of CBD in small human studies likely relate to the activation of TRVP1 receptors. Many other receptors have also been identified to interact with CBD, and further clinical investigation into its possible effects on psychiatric disorders is necessary and underway.
Dosage: How Does CBD Make You Feel?
We know now that a single dose of CBD by itself, no matter how large, cannot cause euphoria or affect your cognition. 1 2 Since CBD does not directly activate CB receptors, this likely explains why consumers don’t experience a “high.” 5
CBD is considered safe and well-tolerated even across a wide dose range. 4 The World Health Organization (WHO) echoes this finding in their latest CBD report and also found no evidence of abuse or dependence potential for CBD. 8
Interestingly, CBD is shown to have essentially the opposite feeling effects of THC. 9 10 When combined, CBD overall tends to reduce the psychological anxiety induced by THC. 11
Nevertheless, these results are a bit mixed, and the ratio doses vary. Follow-up studies done over 12 months on the 1:1 THC:CBD oral spray Sativex® (GW Pharmaceuticals) have shown neither a decline in cognitive function nor a negative mood impact. 12
Long-term, conclusive studies exclusively on CBD and mood are yet to be done. Currently, there is no evidence to support CBD as a mood stabilizer for mood disorders. It is also not yet known how CBD may affect persons who are pregnant or with specific conditions.
To date, the Food and Drug Administration (FDA) has only approved CBD in the form of Epidiolex® (GW Pharmaceuticals) as an anti-seizure medication for rare childhood seizure disorders. A small percentage (<10%) of those study patients reported CBD causing irritability and agitation. 13
CBD Tolerance & Individual Differences
While taking CBD does not cause a “high” that builds a psychological tolerance over time, our bodies may process various CBD dosages and routes differently. CBD may elevate levels of important drugs like blood thinners, antidepressants, seizure medications, and many others due to its interaction with families of significant liver enzymes. 14
In the FDA trials for Epidiolex and in mouse models, high dose CBD (2.5-20 mg/kg) caused high liver enzymes in a small portion of subjects, likely indicating liver damage. 13 15 However, this damage was reversible in two-thirds of Epidiolex patients with dose reduction or cessation if necessary. 13
While such high levels may not be necessary nor practical for the average cannabis plant consumer to achieve or feel the effects they desire, you should always tell your doctor before considering a CBD regimen. They know your medical history and may decide to adjust medication dosages or routinely monitor your liver enzymes.
Never abruptly stop or decrease your prescription medication dose without speaking to your healthcare provider first. Variables like history, height, weight, biological gender, prescriptions, CBD dose, and liver enzyme activity mean that CBD dosing is not an exact science for everyone.
As with consuming THC, CBD should also be dosed in a manner that is “slow and low”– and gradually built up over time if needed. Since there has yet to be established CBD dosing guidelines, a reasonable dose to start would be about 0.1-0.5 mg/kg, meaning an average person of 80kg (176 lbs) should start with a low dose between 8-40mg, and go from there until desired effects are achieved.
The most common side effects of CBD products include: 13
- Diarrhea
- Drowsiness
- High liver enzymes
- Reduced appetite
How Long Does it Take CBD to Work?
Generally, CBD takes effect within a few weeks – but there is some evidence it can also work within hours. The exact answer can’t be known and depends on what your goal of taking it is, in addition to physical and dosing variables.
In a couple of small public speaking studies, CBD in doses of 300mg and 600mg given 90 minutes before stress was able to reduce situational social anxiety. 16 These data are limited and somewhat contradictory since the former study did not find beneficial effects with 600mg of CBD. Therefore, larger investigations are needed to determine proper dosing and indications.
When it comes to depression, previous data is limited, but a new mouse model study found CBD produced rapid antidepressant effects within 30 mins at doses of 7-30mg/kg. 17 18 Of course, it’s still too early to prove anything conclusive in humans, and you should never stop taking antidepressants on your own without speaking to your provider first.
In a large case series of patients with anxiety and sleep issues, subjective improvement in these categories was observed after the first month and sustained until the end of the third month. 19 Note that this was not a well-controlled clinical trial – there was no placebo group for comparison and the people involved knew they were taking CBD (an “open-label” study), leaving room for bias.
Epidiolex patients also saw improvements in seizures within 4 weeks. 13 If you are new to CBD, taking small-moderate doses regularly over several weeks may be useful for your wellness.
Several factors influence how CBD will make you feel. Whether you take CBD gummies or try lollipops, it’s important to check with a healthcare professional before upping your dosage.
Frequently Asked Questions
A healthy consumer would likely say, “Nothing!” Data shows CBD is non-intoxicating and has generally opposite effects of THC. CBD is of special research interest for multiple conditions including psychiatric afflictions – but has yet to be confirmed.
So far, the only approved clinical indications for taking CBD are the rare childhood seizure disorders called Lennox-Gastaut and Dravet syndrome. Other individuals may take CBD as a potentially alleviating and anecdotally beneficial compound to improve their subjective wellbeing – notwithstanding only having promising, yet pre-clinical data at this time.
Science References
- Martin-Santos, R., a Crippa, J., Batalla, A., Bhattacharyya, S., Atakan, Z., Borgwardt, S., … & Zuardi, A. W. (2012). Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers. Current pharmaceutical design, 18(32), 4966-4979.
- Grotenhermen, F., Russo, E., & Zuardi, A. W. (2017). Even High Doses of Oral Cannabidiol Do Not Cause THC-Like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research 2016; 1 (1): 102–112; DOI: 10.1089/can. 2015.0004. Cannabis and cannabinoid research, 2(1), 1-4.
- Campos, A. C., Moreira, F. A., Gomes, F. V., Del Bel, E. A., & Guimaraes, F. S. (2012). Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philosophical Transactions of the Royal Society B: Biological Sciences, 367(1607), 3364-3378
- Crippa, J. A., Guimarães, F. S., Campos, A. C., & Zuardi, A. W. (2018). Translational investigation of the therapeutic potential of cannabidiol (CBD): toward a new age. Frontiers in immunology, 9, 2009.
- DOH DCRx. (2015). An Introduction to the Biochemistry & Pharmacology of Medical Cannabis. [PowerPoint Slides]. Retrieved from: https://dchealth.dc.gov/dcrx
- Blessing, E. M., Steenkamp, M. M., Manzanares, J., & Marmar, C. R. (2015). Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics, 12(4), 825-836.
- Sales, A. J., Fogaça, M. V., Sartim, A. G., Pereira, V. S., Wegener, G., Guimarães, F. S., & Joca, S. R. (2019). Cannabidiol induces rapid and sustained antidepressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Molecular neurobiology, 56(2), 1070-1081.
- Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. British journal of pharmacology, 163(7), 1344-1364.
- Zuardi, A. W., Shirakawa, I., Finkelfarb, E., & Karniol, I. G. (1982). Action of cannabidiol on the anxiety and other effects produced by Δ 9-THC in normal subjects. Psychopharmacology, 76(3), 245-250.
- Freeman, A. M., Petrilli, K., Lees, R., Hindocha, C., Mokrysz, C., Curran, H. V., … & Freeman, T. P. (2019). How does cannabidiol (CBD) influence the acute effects of delta-9-tetrahydrocannabinol (THC) in humans? A systematic review. Neuroscience & Biobehavioral Reviews.
- Rekand, T. (2014). THC: CBD spray and MS spasticity symptoms: data from latest studies. European neurology, 71(Suppl. 1), 4-9.
- GW Pharmaceuticals, Inc. (2018). Epidiolex [package insert].
- Fugh-Berman, A., Wood, S., Kogan, M., Abrams, D., Mathre, M. L., Robie, A., … & Kasimu-Graham, J. (2019). Medical cannabis adverse effects & drug interactions. Government of the District of Columbia: Department of Health.
- Ewing, L. E., Skinner, C. M., Quick, C. M., Kennon-McGill, S., McGill, M. R., Walker, L. A., … & Koturbash, I. (2019). Hepatotoxicity of a cannabidiol-rich cannabis extract in the mouse model. Molecules, 24(9), 1694.
- Linares, I. M., Zuardi, A. W., Pereira, L. C., Queiroz, R. H., Mechoulam, R., Guimaraes, F. S., & Crippa, J. A. (2019). Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Brazilian Journal of Psychiatry, 41(1), 9-14.
- Bergamaschi, M. M., Queiroz, R. H. C., Chagas, M. H. N., De Oliveira, D. C. G., De Martinis, B. S., Kapczinski, F., … & Martín-Santos, R. (2011). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology, 36(6), 1219-1226
- National Academies of Sciences, Engineering, and Medicine. (2017). The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. National Academies Press.
- Shannon, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in anxiety and sleep: a large case series. The Permanente Journal, 23.
- Zuardi, A. W. (2008). Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Brazilian Journal of Psychiatry, 30(3), 271-280.
- Zanelati, T. V., Biojone, C., Moreira, F. A., Guimarães, F. S., & Joca, S. R. (2010). Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. British journal of pharmacology, 159(1), 122–128. https://doi.org/10.1111/j.1476-5381.2009.00521.x
- Boggs, D. L., Nguyen, J. D., Morgenson, D., Taffe, M. A., & Ranganathan, M. (2018). Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 43(1), 142–154. https://doi.org/10.1038/npp.2017.209
- Giuffrida, A., Leweke, F. M., Gerth, C. W., Schreiber, D., Koethe, D., Faulhaber, J., Klosterkötter, J., & Piomelli, D. (2004). Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 29(11), 2108–2114. https://doi.org/10.1038/sj.npp.1300558