Side effects Research indicates that cannabidiol may reduce adverse effects of THC, particularly those causing intoxication and sedation, but only at high doses. Safety studies of cannabidiol showed it is well tolerated, but may cause tiredness, somnolence, sedation, diarrhea, or changes in appetite as common adverse effects with the most common being somnolence and sedation. Side effects of CBD are dose related. Epidiolex documentation lists sleepiness, insomnia and poor quality sleep, decreased appetite, diarrhea, and fatigue. Potential interactions Laboratory evidence indicated that cannabidiol may reduce THC clearance, increasing plasma concentrations which may raise THC availability to receptors and enhance its effect in a dose-dependent manner. In vitro, cannabidiol inhibited the activity of voltage-dependent sodium and potassium channels, which may affect neural activity. A recent study using X-ray crystallography showed that CBD binds inside the sodium channel pore at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition, which could contribute to a reduced excitability. A small clinical trial reported that CBD partially inhibited the CYP2C-catalyzed hydroxylation of THC to 11-OH-THC. Little is known about potential drug interactions, but CBD mediates a decrease in clobazam metabolism. Work with human liver microsomes shows that cannabidiol inhibits CYP3A5 and CYP3A4 to some degree. Veterinary medicine Research The number of research projects and scientific publications on cannabidiol and other cannabinoids in pets surged in the late 2010s; nonetheless, , there were no hemp-derived, cannabinoid-rich registered veterinary medicinal products in any of the major regions (see #Legal status). In the US and other territories there are, however, numerous veterinary nutraceutical products available over the counter (OTC). The lack of clarity in the regulations governing veterinary hemp food supplements allows for products of questionable quality to flood the market, which may pose a risk to the wellbeing of pets and owners. To understand better the benefits of CBD and associated compounds for the quality of life of animals, companies specialized in CBD products for animals have been funding research projects. Canine osteoarthritis CBD's ability to help regulate the endocannabinoid system and reduce the release of excitatory neurotransmitters could result in a retrograde inhibitory signal that lessens chronic pain responses. Studies in dogs with chronic pain associated with osteoarthritis showed an increase in level of activity in animals receiving CBD-rich food