Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test

Linares, Ila Marques Porto; Zuardi, Antônio Waldo; Pereira, Luís; Queiróz, Regina Helena Costa; Mechoulam, Raphael; Guimarães, Francisco Silveira; Crippa, José Alexandre de Souza

doi:10.1590/1516-4446-2017-0015

Cited by 185 publications

(130 citation statements)

References 41 publications

(64 reference statements)

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“…Zuardi and his colleagues used a test that simulates speaking in public to show that pretreatment with a single dose of CBD can reduce the associated discomfort in people with social anxiety disorder 11 . A similar effect has been observed in healthy people in anxiety-inducing situations 12 , and several researchers are exploring CBD as a means of soothing social stress in people with autism spectrum disorder. Devinsky notes that many of his patients with epilepsy have also been diagnosed with autism spectrum disorder, and he is involved in two clinical trials that aim to test whether CBD can meaningfully reduce the irritability and anxiety of those with autism.…”

Section: Multitasking Moleculesupporting

confidence: 56%

The reality behind cannabidiol’s medical hype

Eisenstein¹

2019

Nature

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C annabidiol (CBD) is an illegal drug with no redeeming value. It is also a useful prescription medicine for epilepsy, with considerable potential for treating numerous other conditions. And it is a natural dietary supplement or 'nutraceutical' with countless evangelists in the health and wellness community. Although contradictory, all three statements are true from different perspectives, and clinical researchers are frustrated. "In New York City, you can go to a latte shop and get a CBD product, but if I want to do a clinical trial, I've got to get a 2,000-pound safe and go through six months of paperwork and licensing, " says Orrin Devinsky, director of the NYU Langone Comprehensive Epilepsy Center in New York City. Like the cannabis plant from which it is derived, CBD, a type of cannabinoid, is classified by the US Drug Enforcement Administration in the same way as are heroin and lysergic acid diethylamide (LSD)schedule 1 substances with "high potential for abuse" and "no currently accepted medical use". This flies in the face of current evidence. Numerous studies have shown that CBD is a safe and non-habit-forming substance that does not produce the 'high' associated with tetrahydrocannabinol (THC), the main psychoactive component of cannabis 1. In 2018, the US Food and Drug Administration (FDA) determined that Epidiolex-a purified CBD product developed by GW Pharmaceuticals in Histon, UK-effectively reduces the frequency of seizures in certain rare forms of paediatric epilepsy. This approval has heartened the cannabinoid research community, which has long recognized the medicinal potential of CBD but DRUG REGULATION From menace to medicine Cannabidiol could offer an effective treatment for a variety of conditions. But the substance's uncertain legal status is stalling serious investigation. Cannabidiol oil has purported health benefits, including helping to relieve chronic pain.

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Section: Multitasking Moleculesupporting

confidence: 56%

The reality behind cannabidiol’s medical hype

Eisenstein¹

2019

Nature

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“…The anxiolytic effects of CBD are described in the literature. 13,17,18 The TGA has published a series of clinical guidance documents that summarise the available evidence for medicinal cannabis products in chronic pain, palliative care, epilepsy, spasticity in multiple sclerosis and chemotherapy-induced nausea and vomiting. However, definitive evidence in support of specific medicinal cannabis products for various conditions is often not available.…”

Section: Conditions Treatedmentioning

confidence: 99%

Prescribing medicinal cannabis

2020

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The Australian Federal Government legalised access to medicinal cannabis in 2016. More than 100 different cannabis products are now available to prescribe. Most are oral preparations (oils) or capsules containing delta-9-tetrahydrocannabinol or cannabidiol. Driedflower products are also available. As most products are unregistered drugs, prescribing requires approval under the Therapeutic Goods Administration Special Access Scheme-B or Authorised Prescriber Scheme. Special Access Scheme Category B applications can be made online, with approval usually being given within 24-48 hours. However, supply chain problems may delay dispensing by the pharmacy. By the end of 2019, over 28,000 prescribing approvals had been issued to patients, involving more than 1400 doctors, mostly GPs. More than 70,000 approvals are projected by the end of 2020. Most prescriptions are for chronic non-cancer pain, anxiety, cancer-related symptoms, epilepsy and other neurological disorders. However, the evidence supporting some indications is limited. Many doctors are cautious about prescribing cannabis. While serious adverse events are rare, there are legitimate concerns around driving, cognitive impairment and drug dependence with products containing delta-9-tetrahydrocannabinol. Cannabidiol-only products pose fewer risks. What is medicinal cannabis? The cannabis plant contains hundreds of bioactive molecules, most of which are as yet uncharacterised. The two best studied cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is responsible for the intoxicating effects of cannabis due to its action on CB1 cannabinoid receptors. 6 Despite intoxicating effects at higher doses, clinical trial evidence generally supports the efficacy of THC in treating conditions such as chronic pain, spasticity in multiple sclerosis, anorexia and cachexia, Tourette syndrome and chemotherapyinduced nausea and vomiting. 7,8 Trials currently underway will help to better define the role of THC as a therapeutic across these and other conditions. 9,10 CBD has a very wide range of pharmacological actions but no intoxicating effects. Early evidence suggests therapeutic actions of CBD at relatively high doses (300-1500 mg) in treating epilepsy, anxiety and psychosis. 11-13 Numerous clinical trials are underway for other conditions such as neuropathic pain, drug and alcohol dependence and neurodegenerative disorders. In many countries, CBD is readily available in over-thecounter nutraceutical 'wellness' products. These contain very low doses (e.g. 5-25 mg) for which there is little current evidence of health benefits. Over-the-counter access to CBD is not yet available in Australia, although Jonathon C Arnold Deputy academic director, Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre 1

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“…For example, some effects of CBD seem to have an inverted U-shaped dose–response curve. Regarding anxiety, while a dose superior to 20 mg/kg appears to be ineffective in animals (Guimarhes et al, 1990), a human study with a Simulating Public Speaking Test confirmed this U-shaped dose–response, with an efficacy observed with 300 mg of CBD, but not with 150 mg or 900 mg (Linares et al, 2016). However, other animal studies found an anxiolytic effect with repetitive doses of 30 mg/kg, which may activate different pathways (Campos et al, 2013; Fogaça et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain

Ternay¹,

Naassila

Nourredine³

et al. 2019

Front. Pharmacol.

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Background: Cannabidiol (CBD) is a natural component of cannabis that possesses a widespread and complex immunomodulatory, antioxidant, anxiolytic, and antiepileptic properties. Much experimental data suggest that CBD could be used for various purposes in alcohol use disorder (AUD) and alcohol-related damage on the brain and the liver. Aim: To provide a rationale for using CBD to treat human subjects with AUD, based on the findings of experimental studies. Methods: Narrative review of studies pertaining to the assessment of CBD efficiency on drinking reduction, or on the improvement of any aspect of alcohol-related toxicity in AUD. Results: Experimental studies find that CBD reduces the overall level of alcohol drinking in animal models of AUD by reducing ethanol intake, motivation for ethanol, relapse, anxiety, and impulsivity. Moreover, CBD reduces alcohol-related steatosis and fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, and by inducing death of activated hepatic stellate cells. Finally, CBD reduces alcohol-related brain damage, preventing neuronal loss by its antioxidant and immunomodulatory properties. Conclusions: CBD could directly reduce alcohol drinking in subjects with AUD. Any other applications warrant human trials in this population. By reducing alcohol-related steatosis processes in the liver, and alcohol-related brain damage, CBD could improve both hepatic and neurocognitive outcomes in subjects with AUD, regardless of the individual’s drinking trajectory. This might pave the way for testing new harm reduction approaches in AUD, in order to protect the organs of subjects with an ongoing AUD.

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Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test

Cited by 185 publications

References 41 publications

The reality behind cannabidiol’s medical hype

The reality behind cannabidiol’s medical hype

Prescribing medicinal cannabis

Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain

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