CBD is technically an unregulated substance in the United States and therefore it ought to be used with caution. This is especially important for those taking additional medications and/or those with ongoing medical issues. That said, preliminary research on CBD and its benefits are promising in relation to helping with mild to moderate health concerns and it is generally considered a safe substance. Health professionals do not consider CBD a cure-all for serious medical issues, including cancer.
Also known as “cotton mouth,” CBD can potentially cause your mouth and eyes to feel very dry. Though this side effect is more likely to occur with THC, it can happen with CBD as well.
The most comment side effects of CBD include drowsiness, gastrointestinal issues, dry mouth, reduced appetite, nausea, and interaction with other medications. Those are outlined in detail below.
CBD is one of the many chemical compounds that is found in the cannabis plant—referred to as cannabis sativa. There are two primary parts of the plant that humans use. One is THC, or Delta-9-Tetrahydrocannabinol, and the other is CBD. Though they’re from the same plant, THC and CBD are quite different from each other.
CBD Is Still an Unregulated Substance
CBD might interfere with the other medications you take. Dr. Matharu-Daley says it’s important to talk to your doctor about whether CBD could affect your existing prescriptions.
Some people may get diarrhea or liver problems [when using CBD]. This is dependent on the individual and their medical history, so monitoring is important,” says Dr. Matharu-Daley.
There are several reasons why someone might want to use CBD. The substance can be found in a multitude of products ranging from pain-relieving creams to edible tinctures to skincare. Research is still underway, but over the last few decades scientists have become more aware of how CBD might be beneficial when applied either topically or ingested.
Karen Cilli is a fact-checker for Verywell Mind. She has an extensive background in research, with 33 years of experience as a reference librarian and educator.
Ultimately, the primary reasons why people use CBD is because it tends to have calming, relaxing, pain-reducing effects. It has been used to alleviate joint pain and nerve pain, reduce anxiety and stress, treat insomnia, improve migraines, and address nausea.
Considerable evidence demonstrates that manipulation of the endocannabinoid system regulates nausea and vomiting in humans and other animals. The anti-emetic effect of cannabinoids has been shown across a wide variety of animals that are capable of vomiting in response to a toxic challenge. CB(1) agonism suppresses vomiting, which is reversed by CB(1) antagonism, and CB(1) inverse agonism promotes vomiting. Recently, evidence from animal experiments suggests that cannabinoids may be especially useful in treating the more difficult to control symptoms of nausea and anticipatory nausea in chemotherapy patients, which are less well controlled by the currently available conventional pharmaceutical agents. Although rats and mice are incapable of vomiting, they display a distinctive conditioned gaping response when re-exposed to cues (flavours or contexts) paired with a nauseating treatment. Cannabinoid agonists (Δ(9) -THC, HU-210) and the fatty acid amide hydrolase (FAAH) inhibitor, URB-597, suppress conditioned gaping reactions (nausea) in rats as they suppress vomiting in emetic species. Inverse agonists, but not neutral antagonists, of the CB(1) receptor promote nausea, and at subthreshold doses potentiate nausea produced by other toxins (LiCl). The primary non-psychoactive compound in cannabis, cannabidiol (CBD), also suppresses nausea and vomiting within a limited dose range. The anti-nausea/anti-emetic effects of CBD may be mediated by indirect activation of somatodendritic 5-HT(1A) receptors in the dorsal raphe nucleus; activation of these autoreceptors reduces the release of 5-HT in terminal forebrain regions. Preclinical research indicates that cannabinioids, including CBD, may be effective clinically for treating both nausea and vomiting produced by chemotherapy or other therapeutic treatments.
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Recently, our laboratory has investigated the mechanism of action for the anti-emetic effects of CBD. Consistent with previous results, CBD (5 mg·kg −1 , s.c.) was shown to be effective in suppressing vomiting in the S. murinus induced by either nicotine, LiCl or cisplatin (20 mg·kg −1 , but not 40 mg·kg −1 ). Interestingly, this CBD-induced suppression of vomiting was reversed by systemic pretreatment with the 5-HT1A antagonist WAY100135 (E.M. Rock et al., unpubl. obs.), suggesting that the anti-emetic effect of CBD may be mediated by activation of somatodendritic autoreceptors. This activation of the 5-HT1A receptors results in a reduction of the rate of firing of 5-HT neurones, ultimately reducing the release of forebrain 5-HT (Blier and de Montigny, 1987). It is this reduction in 5-HT release that is probably mediating CBD’s anti-emetic effects. In addition, a recent finding suggests that CBD may also act as an allosteric modulator of the 5-HT3 receptor (Yang et al., 2010); CBD reversibly inhibited 5-HT-evoked currents in 5-HT3A receptors expressed in Xenopus laevis oocytes in a concentration-dependent manner (1 µM), but did not alter the specific binding of a 5-HT3A antagonist. These findings suggest that allosteric inhibition of 5-HT3 receptors by CBD may also contribute to its role in the modulation of emesis.
The cannabis plant has been used for several centuries for a number of therapeutic applications (Mechoulam, 2005), including the attenuation of nausea and vomiting. Ineffective treatment of chemotherapy-induced nausea and vomiting prompted oncologists to investigate the anti-emetic properties of cannabinoids in the late 1970s and early 1980s, before the discovery of the 5-HT3 antagonists. The first cannabinoid agonist, nabilone (Cesamet), which is a synthetic analogue of Δ 9 -THC was specifically licensed for the suppression of nausea and vomiting produced by chemotherapy. Furthermore, synthetic Δ 9 -THC, dronabinol, entered the clinic as Marinol in 1985 as an anti-emetic and in 1992 as an appetite stimulant (Pertwee, 2009). In these early studies, several clinical trials compared the effectiveness of Δ 9 -THC with placebo or other anti-emetic drugs. Comparisons of oral Δ 9 -THC with existing anti-emetic agents generally indicated that Δ 9 -THC was at least as effective as the dopamine antagonists, such as prochlorperazine (Carey et al., 1983; Ungerleider et al., 1984; Crawford and Buckman, 1986; Cunningham et al., 1988; Tramer et al., 2001; Layeeque et al., 2006).
A major advance in the control of acute emesis in chemotherapy treatment was the finding that blockade of one subtype of the 5-hydroxytryptamine (5-HT) receptor, the 5-HT3 receptor, could suppress the acute emetic response (retching and vomiting) induced by cisplatin in the ferret and the shrew (Costall et al., 1986; Miner and Sanger, 1986; Ueno et al., 1987; Matsuki et al., 1988; Torii et al., 1991). In clinical trials with humans, treatment with 5-HT3 antagonists often combined with the corticosteroid dexamethasone during the first chemotherapy treatment reduced the incidence of acute vomiting by approximately 70% (e.g. Bartlett and Koczwara, 2002; Aapro et al., 2003; Ballatori and Roila, 2003; Hickok et al., 2003; Andrews and Horn, 2006). However, the 5-HT3 antagonists are less effective at suppressing acute nausea than they are at suppressing acute vomiting (Morrow and Dobkin, 1988; Bartlett and Koczwara, 2002; Hickok et al., 2003) and they are ineffective at reducing instances of delayed (24 h later) nausea and vomiting (Morrow and Dobkin, 1988; Grelot et al., 1995; Rudd et al., 1996; Rudd and Naylor, 1996; Tsukada et al., 2001; Hesketh et al., 2003) and anticipatory (conditioned) nausea and vomiting (Nesse et al., 1980; Morrow and Dobkin, 1988; Hickok et al., 2003).
Effects of cannabinoids on nausea in animal models
Over the past number of years, our laboratory has provided considerable evidence that conditioned nausea in rats may be displayed as conditioned disgust reactions (Parker, 1982; 1995; 1998; 2003; Limebeer and Parker, 2000; 2003; Limebeer et al., 2004; Parker et al., 2008; 2009b;) using the taste reactivity (TR) test (Grill and Norgren, 1978). Rats display a distinctive pattern of disgust reactions (including gaping, chin rubbing and paw treading) when they are intraorally infused with a bitter tasting quinine solution. Rats also display this disgust pattern when infused with a sweet tasting solution (that normally elicits hedonic reactions of tongue protrusions) that has previously been paired with a drug that produces vomiting (such as LiCl or cyclophosphamide) in species capable of vomiting. Only drugs with emetic properties produce this conditioned disgust reaction when paired with a taste.
The typical measure used in the literature to evaluate the nauseating potential of a drug is conditioned taste avoidance. However, taste avoidance is not only produced by nauseating doses of drugs, it is also produced by drugs that animals choose to self-administer or that establish a preference for a distinctive location (e.g. Berger, 1972; Wise et al., 1976; Reicher and Holman, 1977). In fact, when a taste is presented prior to a drug self-administration session, the strength of subsequent avoidance of the taste is a direct function of intake of the drug during the self-administration session (Wise et al., 1976; Grigson and Twining, 2002). This paradoxical phenomenon was initially interpreted as another instance of taste aversion learning. Because Garcia et al. (1974) had developed a model to account for taste aversion produced by emetic agents, it was reasonable for early investigators to assume that rewarding doses of drugs also produce taste avoidance because they produce a side effect of nausea that becomes selectively associated with a flavour (Reicher and Holman, 1977). However, in an animal capable of vomiting, the S. murinus, rewarding drugs do not produce a conditioned taste avoidance, in fact they produce a conditioned taste preference and a conditioned place preference (Parker et al., 2002a). Since rats are incapable of vomiting, it is likely that conditioned taste avoidance produced by rewarding drugs in this species is based upon a learned fear of anything that changes their hedonic state (e.g. Gamzu, 1977) when that change is paired with food previously eaten.
A relative of the cannabinoid system, vanilloid TRPV1 receptors have recently been shown to regulate emesis in the ferret (Sharkey et al., 2007). The TRPV1 receptor is targeted by capsaicin (the burning component of chili peppers) as well as resiniferatoxin, which can produce pro-emetic and anti-emetic effects at similar doses in S. murinus (Andrews et al., 2000), but produces anti-emetic effects in ferrets (Andrews and Bhandari, 1993; Andrews et al., 2000; Yamakuni et al., 2002). Recent evidence indicates that anandamide and the endovanniloid, N-arachidonoyl-dopamine (NADA), are endogenous agonists for both CB1 and TRPV1 receptors (Di Marzo and Fontana, 1995; van der Stelt and DiMarzo, 2004). Extensive colocalization of CB1 and TRPV1 receptors have been demonstrated (Cristino et al., 2006). Both endogenous (anandamide, NADA) and synthetic (arvanil or O-1861) ‘hybrid’ agonists of CB1 and TRPV1 receptors have been shown to exert more potent pharmacological effects in vivo (Di Marzo et al., 2001) than ‘pure’ agonists of each receptor type, particularly when acting on cells co-expressing the two receptor types (Hermann et al., 2003). Sharkey et al. (2007) found that anandamide, NADA and arvanil were all anti-emetic in the ferret; these effects were attenuated by the CB1 receptor inverse agonist AM251 and the TRPV1 antagonists iodoresiniferatoxin and AMG9810. TRPV1 receptors were localized in the ferret NTS and were co-localized with CB1 in the mouse brainstem.
At doses (greater than 4 mg·kg −1 ) that effectively suppress feeding in rats, the CB1 antagonist/inverse agonist AM251 produces conditioned gaping reactions when explicitly paired with saccharin solution (McLaughlin et al., 2005) reflective of nausea. This finding suggests that the appetite suppressant effect of the newly marketed CB1 antagonist/inverse agonist, rimonabant, may be partially mediated by the side effect of nausea, which is the most commonly reported side effect in human randomized control trials (Pi-Sunyer et al., 2006). On the other hand, the silent CB1 antagonists, AM4113 and AM6527, which do not have inverse agonist properties, do not produce conditioned gaping (Sink et al., 2007; Limebeer et al., 2010). In addition, the peripherally restricted silent CB1 antagonist, AM6545, which also suppresses feeding at equivalent doses of AM251 (Cluny et al., 2010; Randall et al., 2010; Tam et al., 2010), does not produce the side effect of nausea (Cluny et al., 2010). Finally, neither the silent antagonist, AM6527 (which crosses the blood–brain barrier) nor AM6545 (with limited CNS penetration), potentiate LiCl-induced nausea, an effect evident with low doses (2.5 mg·kg −1 ) of systemic administration of AM-251 (Limebeer et al., 2010). AM251-induced conditioned nausea is thus mediated by inverse agonism of the CB1 receptor. This effect may be mediated peripherally, because intracranial administration of AM251 at doses up to 1/10 the peripheral dose into the lateral ventricle or the 4th ventricle did not potentiate LiCl-induced nausea that is evident with systemic administration of this inverse agonist of the CB1 receptor.