The Impact of Cannabidiol on Psychiatric and Medical Conditions
c Corresponding Author: Thersilla Oberbarnscheidt, Department of Psychiatry, Western Psychiatric Hospital, University of Pittsburgh, UPMC Health, Pittsburgh, PA, USA. Email: [email protected]
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The authors declare that data supporting the findings of this study are available within the article.
Cannabidiol (CBD) is a substance chemically derived from Cannabis sativa and discussed to be non-psychoactive. According to the FDA, marijuana is classified as a schedule I substance; however, hemp which is defined as extracts from marijuana including cannabinoids containing less than 0.3% tetrahydrocannabinol (THC), is excluded from that controlled substance act and available at local convenience stores in the US as it is seen as an herbal supplement. CBD is purported to be used for various medical and psychiatric conditions: depression, anxiety, post-traumatic stress disorder, Alzheimer’s or other cognitive illnesses as well as pain. There is also a new trend to use CBD for the treatment of opioid use disorder. The one CBD product on the market that is FDA approved for the treatment of childhood epilepsy forms Dravet and Lennox-Gastaut syndromes is available under the name Epidiolex. There is a significant difference between this medication and the over-the-counter CBD products that contain very inconsistent strengths of CBD, if they contain it at all, and vary in percentage even from sample to sample. Frequently the so-called CBD products are not containing any CBD at all, but mostly containing THC. This article is a systematic review of literature reviewing the available clinical data on CBD, for use in various medical and psychiatric conditions with focus on a review of the pharmacology and toxicity. Resources used were ORVID, PubMed, MEDLINE, PsychINFO, EMBASE with keywords CBD, cannabidiol, hemp and cannabinoids.
CBD, also called cannabidiol, is chemically derived from hemp (Cannabis sativa), which is the most commonly used illicit drug both nationally and internationally .
It was first obtained from American hemp and Egyptian hashish in 1940 . In its natural form cannabis consists of the two most well-known active chemicals tetrahydrocannabinol (THC) and CBD as well as about 480 other active cannabinoids (CBs) that are not yet well researched. The THC in the cannabis is the psychoactive ingredient with toxicity. The THC content in a product labeled as CBD is supposed to contain less than 0.3% dry weight of THC in its leaves and buds .
Even though CBD use is a global problem, this article will focus on the current situation and trend within the US. Marijuana as well as CBD is purported for use in the US for the self-treatment of numerous medical and psychiatric conditions as a so-called “medicine”. It is commonly used for depression, anxiety, seizures, nausea, appetite enhancer, anti-inflammatory, pain or the new trend to self-treat opioid use disorder .
Against the usual course of a medication development, both substances have not been scientifically investigated or developed prior to their use, but were determined by claims in the general public of their medicinal value . Possible toxic effects and drug-drug interactions should be considered, and consumers should be educated about the risks and safety concerns regarding this substance, which are currently not publicized.
Due to CBD being exempt from federal regulations by the in 2018 passed US farm bill, it is easily accessible and available at convenience stores throughout the US .
The sale and marketing of CBD and CBD-containing products are very important economic factors as sales reached $2 billion US dollars in 2018 and are rising .
Of the US population, 9% of the people less than 35 years of age reported the use of CBD at least once, 6.4% of the people between 45 and 55 years and 3.7% of the people over 55 years of age .
The question for public health is if CBD is really non-psychoactive and as safe as it is advertised in the general-public?
Pharmacological Action of CBD
CBD can be ingested in various routes. It is available in the form of oils, lotions, edibles, teas or smoked ( Figs. 1 , ,2) 2 ) . It is rarely administered intravenously but that route is possible .
CBD chemical structure (source: PUBCHEM ). CBD: cannabidiol.
Chemical structure of THC for comparison (source: PUBCHEM ). THC: tetrahydrocannabinol.
CBD undergoes a significant first pass metabolism in the liver after ingestion. The bioavailability after oral consumption is estimated 6%, and after smoking is estimated to be about 6-31% .
CBD’s primary active metabolite is 7-hydroxy-CBD (7-OH-CBD) . The half-life of CBD depends on the route of administration. Smoked, the half-life is about 27 – 35 h, after oral ingestion 2 – 5 days and the shortest after intravenous injection with about 18 – 33 h .
CBD is very lipophilic, similar to cannabis, and easily passes the blood-brain barrier. It gets quickly distributed into adipose tissue and other organs. Due to its lipophilic quality, CBD accumulates in the adipose tissue particularly in patients with high adiposity and is redistributed into the circulation at a later point . The amount used varies in a wide spectrum: administered doses in studies range from 5 – 1,500 mg/day orally up to 30 mg intravenously .
CBD does bind to the CB receptors, normally activated by endogenous CBs including anandamide and 2-arachidonylglycerol. There are two specific CB receptors identified. Unlike THC that binds to CB1 receptors that are mostly located in the brain, CBD binds mostly to CB2 receptors that are found on cells of the immune system, which include T and B lymphocytes, macrophages and monocytes which are not as highly expressed in the central nervous system .
The activation of those receptors decreases the release of neurotransmitters glutamate, gamma-aminobutyric acid (GABA), serotonin and norepinephrine and provides synaptic control of upstream neurotransmission [17-19].
CBD acts on several other receptor types. Those include receptors of the serotonin system 5HT 1A/2A/3A, glutamate, TRPV-a (vanilloid) receptors, agonist activity on alpha-1 adrenergic receptors as well as mu-opioid receptors .
In addition, CBD acts on the adenosine levels by reducing the adenosine reuptake, which has been associated with neuroprotection and anti-inflammatory processes in the brain .
CBD also acts directly on the cerebral vasculature by inhibiting the nitric oxide synthase protein expression as well as inhibition of calcium transport across membranes. Through this mechanism it causes vasodilatation .
CBD has shown in vitro studies to be a potent inhibitor with cytochrome P450 enzymes such as CYP1A2, CYP2B6, CYP2C9, CYP2D6 and CYP3A4 [23-36]. These enzymes are also responsible for the metabolization of various other medications. Therefore, CBD will most likely interfere with the serum levels of other medications such as antibiotics, antipsychotics, antidepressants and blood thinners as well as many more. Studies about these interactions are yet lacking. The interactions with CBD and other medications are summarized in Table 1 [23-36].
|Enzyme||Medication that interacts||Effect|
|CYP3A4 substrate||Immunosuppressants, antidepressants, opioids, statins, benzodiazepines||Increases toxic effects/levels of substrate|
|CYP3A4 inhibitor||Ketoconazole, loperamide, nefazodone, cimetidine, verapamil||Increases level/toxicity of CBD|
|CYP3A4 inducer||Phenytoin, topiramate, carbamazepine, rifampicin, efavirenz, pioglitazone||Decreases bioavailability of CBD
Reduces effect/level of CBD
|CYP2C19 substrate||Proton pump inhibitor, antidepressants, antiepileptics, clopidogrel, propranolol, warfarin, cyclophosphamide||Increases toxic effects/level of substrate|
|CYP2C19 inhibitor||Cimetidine, proton pump inhibitors, fluvoxamine, clopidogrel, fluconazole||Increases level/toxicity of CBD|
|CYP2C19 inducer||Phenobarbital, phenytoin, St. John’s Wort, rifampicin, carbamazepine||Decreases bioavailability of CBD
Reduces effect/level of CBD
|CYP2C8/9||Buprenorphine, montelukast, celecoxib, phenobarbital, phenytoin, warfarin, valsartan||Increases toxic effects/levels of substrate|
It is possible to ingest quantities of CBD that will cause a fatal overdose but very large doses are required for that to occur in human . The toxicity levels for CBD can be found in the federal government’s Toxicology Data Network . The lethality risk with toxic substances is usually measured in the LD50 which is the amount of substance needed to kill 50% of the population .
There are three studies citied regarding the LD50 determination of CBD [37-12]: 1) In 1946, the LD50 for CBD in dogs was determined to be greater than 254 mg per kg of body weight, when administered intravenously. 2) In 1975, an LD50 was established in mice at 50 mg per kg of body weight, when administered intravenously. 3) In 1981, a report in Toxicology and Applied Pharmacology showed the LD50 for CBD to be 212 mg per kg of body weight when administered intravenously in monkeys.
More recently, a 2011 article in the journal “Current Drug Safety” observed toxic levels of CBD in rhesus monkeys when administered orally. Doses over 200 mg per kg of body weight proved to be fatal in some monkeys by way of respiratory arrest and cardiac failure, while 300 mg per kg of body weight resulted in “rapid death” .
For reference, consider a relatively “average sized” human at 75 kg (approximately 165 lbs). By these numbers, it would take roughly 18,750 mg (18.75 g) of CBD consumed within a very short amount of time to result in any potentially fatal effects. By comparison, most typical CBD oil users consume no more than 100 mg of the compound, and that is throughout the course of an entire day .
CBD’s Effect on Medical and Psychiatric Conditions
Table 2 [14, 42-85] gives an overview of the toxic effects of CBD that are further discussed more in detail.
Some of the listed effects are more acute in nature, and others are more chronic.
Anaphylaxis and rashes are usually occurring immediately after ingestion. Also, dizziness as well as vomiting, diarrhea and dry mouth occur shortly after ingestion.
Depending on the route of ingestion, the toxic effects occur faster with increased bio-availability. The effects on mood and thoughts as well as sleep and immune-system will be discussed more in detail below. The toxic effects can occur even with very small doses of CBD depending on the user’s sensitivity but are more like to occur in higher doses. Users with impaired liver function are at higher risk to experience toxic effects than healthy individuals. There are no data available yet to differentiate reliably between the risks of different age groups, gender or ethnicity.
Anxiety/post-traumatic stress disorder (PTSD)
Anxiety and PTSD are very common psychiatric disorders in the US and are associated with substance use. While cannabis with its THC content has shown to be anxiogenic during intoxication as well as withdrawal, CBD has been discussed to have some anxiolytic potential [42, 43].
In animal studies, the systemic administration of CBD had caused a decrease in neurons associated with fear (c-Fos positive neurons) and a direct infusion of CBD in the amygdala neurons has led to decreased anxiety-related behaviors . Another animal model showed that CBD modifies the cerebral blood flow in brain areas that play a role in anxiety symptoms: amygdala, hippocampus, hypothalamus as well as cingulate cortex .
Several human studies have shown some positive results of CBD in anxiety conditions as well. The effect of CBD on the amygdala was studied in brain imaging studies and showed a decrease in activation in the amygdala after administration of CBD .
A placebo-controlled study by Crippa et al showed a decrease in social anxiety symptoms but also sedation in a small group of 10 patients receiving CBD. The patients in this clinical study were treatment naive and with 10 participants the study was small .
Another study by Bergamaschi among 24 treatment naive patients looked at the effect of 600 mg CBD during a public speaking test and noticed a reduction in anxiety, cognitive impairment as well as discomfort in speech performance .
Furthermore, a study by Das et al including 48 healthy volunteers was evaluated for anxiety provoking electric shock anticipation and received either pure CBD without THC or placebo. The results showed that CBD increases extinction learning which might play a role in therapeutic approaches for anxiety disorder treatment .
The lifetime prevalence for PTSD in the US is about 6.1% of the population. The treatment has been mostly consistent of antidepressants as well as Prazosin for nightmares. CBD has been reported in case-control studies to be beneficial for nightmare symptoms associated with PTSD .
In another small study of 11 patients with PTSD, oral CBD was administered open-labeled and the patient’s PTSD symptoms were evaluated initially and on consecutive days up to 8 weeks after utilizing the PCL-5 test and score. Ninety-one percent of the patients reported a decrease in nightmare symptoms. None of the patients reported side effects .
However, despite these studies with small patient numbers, utilizing the pure form of CBD, there are also several case reports of CBD-induced anxiety symptoms as a toxic side effect from the substance.
As part of CBD’s ability to control the cerebral neurotransmission of serotonin and norepinephrine and its active binding to 5HT-1 A receptors , CBD is thought to also have an effect on depression. In addition, CBD stimulates the synaptic plasticity and neurogenesis which also plays a role in the development and treatment of depression [17-20].
Some animal models have shown some promising results. A mouse depression model showed significant antidepressant-like effect after administration of CBD. The animals showed increased engagement on pleasurable activities .
However, in humans, there are very limited studies available. In vitro, CBD is found to be a microglial stabilizer which is similar to the medication lithium which could be beneficial for depression and mood stabilization .
In humans, there are only few case studies published of individual patients with a history of depression who have previously been on traditional treatment with selective serotonin reuptake inhibitor (SSRI) who successfully tried CBD products and experienced a significant improvement in their depressive symptoms .
Caution with these studies is warranted. The studies are utilizing a controlled CBD form without any significant THC content, studies have small patient numbers and the follow-up windows are short. Major toxic effects have been reported with the use of CBD, being more depressed one of them and even suicidal ideations [52, 56].
The pack insert of the FDA approved form of CBD Epidiolex lists depression and suicidal ideation as a possible adverse reaction. In the largest placebo-controlled clinical trial among 27,863 patients treated with Epidiolex and 16,029 patients treated with placebo, the risk of suicidal ideations was increased 1 in every 530 patient and four suicides occurred in the Epidiolex treated group versus none in the placebo group .
There are no compatible data available comparing OTC CBD with placebo regarding increased risk of suicidality.
In studies using animal models for schizophrenia, CBD has shown to improve psychotic symptoms . Zuardi et al looked at the effect of CBD on stereotypy induced by dopaminergic agonist in rodents and found that CBD decreased those similarly to haldol . In a mice model, CBD was compared with haloperidol and clozapine and was found to be equivalent in inhibition of the hyperlocomotion induced by amphetamines and ketamines . In comparison to the conventional medication haloperidol and clozapine, CBD did not induce any catatonia, not even in doses as high as 480 mg/kg. Most commonly, doses of 120 – 240 mg/kg were needed to show any effect, which points to a lower potency of CBD .
There are very few and limited studies available in humans. Boggs et al looked at the effect of CBD at 600 mg in schizophrenia and reported that the medication was well tolerated and did not worsen mood or suicidality but was ineffective in treating cognitive impairment and other neuropsychiatric complications of schizophrenia .
Another double-blind, randomized clinical trial compared CBD with amisulpride and noted similar clinical improvement with less side effects . In the study, 33 patients with schizophrenia were followed over a 4-week period and received either amisulpride or CBD. Both patient groups improved similarly utilizing the positive and negative syndrome scale (PANSS) score with some superiority in improvement of the negative symptoms in the CBD group .
Leweke et al conducted a study looking at the effect of CBD on visual hallucinations induced by nabilone in healthy volunteers. CBD showed to decrease the degree in visual hallucinations . This study since it uses a synthetic form of THC to induce psychosis, as well as other research groups, has raised the questions if CBD might have antagonizing effects to the negative psychotropic effects of THC and might be potentially protective of the side effects of THC .
The study populations in these studies are mostly small and the follow-up is short or only monitored in a one-time event. The number of available studies is very limited, and mostly there are individual case reports published [61, 65-67].
Alzheimer’s disease (AD)
CBD has some pharmacological characteristics that might point to be benefit in the treatment of AD. Libro at al showed that CBD is able to prevent the development of amyloid plaques in vitro. The group pre-treated a gingiva tissue sample with CBD and looked at the change in mesenchymal stem cells, meaning that it could possibly be beneficial in the treatment of AD. Also, CBD regulates the expression of GDK3b a central factor implemented in the molecular pathogenesis of AD .
In animal models, CBD has shown to prevent glutamate-induced excitotoxicity and to reduce inflammatory mediators and well as reduce lipid peroxidase. In addition, the active binding to CB2 receptors was causing a down-regulation in microglial activation in animal in vivo studies. In a mouse model with hippocampal gliosis induced by injection of human Aβ-fragment, CBD inhibited the glial cell activation and proinflammatory mediator release in a dose-dependent manner.
In a rat model, CBD stimulated the hippocampal neurogenesis which would technically mean that CBD reverses the disease .
In case reports of traumatic brain injuries, CBD has been found to reduce brain damage after cerebral trauma by improving the metabolic activity . Those findings have been confirmed in magnetic resonance imaging (MRI) and positron emission tomography (PET) studies. Studies are ongoing that evaluate this effect in persons with high risk concussion rates, for example, football players.
CBD has been frequently associated with the side effect of sedation which would be very negative in patients with AD and lead to other medical complications due to decreased activity in this elderly population. More studies need to be done to show efficacy of CBD in AD or other forms of dementia.
Epilepsy and seizures
The use of CBD for the treatment of seizures has been researched since the 1970s. Overall the idea is to utilize CBD’s effect on neuronal hyperactivity which means excessive neuronal firing as it occurs in seizure disorders . The exact mechanism of CBD’s action on epilepsy is unknown. In vitro, CBD has shown to decrease epileptiform local field potentials, their amplitude and duration .
In animal models, predominantly mice, it has shown some positive effects in few studies but no effect in most others. Studies performed in rats by Jones et al have shown anticonvulsant effects in partial pilocarpine and penicillin-induced seizures. In chronic epilepsy studies in animals have been less optimistic, showing little to no effect on the seizure activity .
In humans, the data are very limited for the natural form of CBD. The only FDA approved CBD medication for childhood seizures, Dravet and Lennox-Gastaut syndromes, is Epidiolex, which is a synthetic substance with a purity of 98% CBD and less than 0.15% THC. Difference to the over-the-counter (OTC) CBDs is that Epidiolex is showing the same content of CBD and dose in one unit to the other. The two FDA approved conditions are both very severe and devastating forms of childhood seizures where seizures are most commonly refractory to traditional pharmaceutical treatment forms and children develop encephalopathy with intellectual disability and neurodevelopmental problems early on in their lives [74-77]. Epidiolex is an FDA approved medication, prescribed by physicians, and patients will be evaluated and monitored. In contrast this is not the case with the OTC form of CBD.
Researches regarding the effect of CBD on sleep are still in its infancy. Endocannabinoids have been shown to play a role in the circadian rhythm, therefore CBD is thought to have an effect on sleep [78-80].
In animal models, studies have been performed to show the effect of CBD on the sleep quality as well as the sleep cycle . In rats, studies have shown that high doses of CBD lead to increased total percentage of sleep. In another rodent model, high dose CBD led to increased rapid eye movement (REM) sleep latency, while the low dose CBD showed a decrease with no effect shown on the non-rapid eye movement (NREM) sleep .
Only few and small numbered human studies are available to show the effect of CBD on sleep. The sedating effect of CBD appears to be dose dependent. Low dose of CBD has been found to be more stimulating, while higher doses have a sedating effect. Two studies by Nicholson and Zuadi et al showed that a CBD dose of 160 mg/day to increase sleep time in persons suffering insomnia as well as decrease nightly arousals while a lower dose again showed increased wakefulness [79, 80]. Basic research in humans showed an overall increase in the total amount of sleep with several sleep disorders [79, 80].
There are no data available yet to show the effects of CBD abstinence syndrome on sleep as it is described with THC to cause prolonged insomnia as a symptom or prolonged withdrawal . Long-term and chronic use for insomnia bears the risk for development of dependence to CBD.
From pre-clinical studies, CBD is discussed to have protective effects against striatal degeneration . In animal studies CBD has shown promising capabilities to reduce striatal dopamine hypersensitivity which is mediating chorea [83, 84]. This has been shown predominantly in rats. CBD also reduced the aggressive behaviors in rats treated with neurotoxin L-pyroglutamate which is one possible pathophysiological model for the aggressive behaviors seen in Huntington’s disease .
A genetic mouse model has shown neuroprotective properties of CBD towards the striatal degeneration through selective binding to CB2 receptors .
Few clinical studies have looked at the effect of CBD on Huntington’s disease and not shown beneficial value in the medicinal properties of CBD in the treatment of this devastating disease .
A study done by Consroe et al compared CBD versus placebo. The group used a mean dose of 700 mg CBD daily on 15 patients with Huntington’s disease. The group did not find any significant difference in chorea severity, side effects and lab tests after 6 weeks of treatment .
CBD is commonly used for pain without any scientific evidence nor FDA approval. Preclinical studies have proposed hat CBD might be useful in the treatment of chronic pain conditions .
However, clinical studies have been unconvincing so far. In Naftali’s study, CBD at 10 mg per day dose was shown ineffective in the treatment of Chron’s disease . Also, another study by Ben showed that CBD was ineffective at 40 mg per day dose in the treatment of chronic neuropathic pain. Other people suggested CBD to be useful in the treatment of cancer pain but studies supporting this statement are yet to be done . None of the available studies are long-term and showing relevant beneficial clinical effect to advocate for the use of CBD in pain conditions.
Opioid use disorder (OUD)
In the US approximately 2.5 million people have been diagnosed with an OUD and about 80 people each day die of overdose. OUD is a burden for each individual person, their families and the society. The annual costs associated with OUD are estimated 78 billon US dollars .
The conventional medication assisted treatments available for OUD including methadone, buprenorphine as well as naltrexone, have been of value but also associated with their own challenges. Those medications are regulated and require the person to be enrolled in a treatment program, which is time-consuming and associated with a negative stigma. This bears grounds to investigate for alternatives, easier accessible and less controlled treatment options for OUD .
Blogs on the internet are attracting an increasing number of people with OUD and discuss the use of CBD during withdrawal as well as ongoing maintenance treatment. CBD is advertised as safe and with low lethality even in combination with strong opioid agonists .
In animal studies, CBD has been shown to reduce the rewarding effects of opioids and it also reduces the heroin-seeking behaviors. CBD acts on the same receptors that heroin does and antagonizes the heroin’s effect on CB1 and glutamate receptors .
The data from Colorado are concerning, with the increased use of CBs and THC, there has been a corresponding increase in opioid use and no decrease in opioid use since the legalization [92, 93].
However, there are only limited case reports available in humans regarding the use of CBD in OUD or small numbered clinical studies that are not allowing a broad statement regarding CBD’s efficacy in the treatment of OUD.
The treatment of OUD with CBD bears particularly a risk, as the amount of CBD taken is not dosed in a controlled setting and for someone who has lost control over a substance prior might have difficulties dosing CBD as well.
CBD and addiction
CBD is unlike THC not binding to the cerebral CB1 receptor which is responsible for the rewarding effects of cannabis in its natural form and for the feeling of euphoria. Many articles state that CBD is a non-psycho-active substance [3-5]. However, it must have some degree of psycho-activity if it alters people’s mood, anxiety as well as cognition.
As with many other substances listed in the DSM V for substance use disorders, it is also possible with CBD to experience a loss of control and a compulsive use. Even though the risk of lethality is very low, it does not mean it is impossible to become addicted to the substance [37, 38, 94].
Withdrawal symptoms are not well described in the literature but however, most likely a person who takes CBD regularly for insomnia, will experience rebound insomnia if he stops .
Similar exacerbating effects are to be expected when CBD is no longer taken for depression or anxiety [12, 42]. Studies about the withdrawal symptoms from CBD and their course are yet to be published. Only case reports exist.
Under Federal Law, marijuana is still listed as a schedule I substance which means that the substance is not accepted for medical use and has a high potential for abuse. In comparison, cocaine is a schedule II substance since it is used as an anesthetic medically .
The Drug Enforcement Administration (DEA) has specific criteria for a drug to be considered a medication [3, 6]: 1) The drugs chemistry must be known and reproducible; 2) The drug must have shown efficacy in well-controlled clinical study; 3) The drug must have shown safety; 4) It must be accepted by qualified experts and scientific evidence must be widely available.
CBD falls under the regulation of the “Farm Bill” (the agriculture improvement act of 2018, Pub. L. 115-334) which was signed in December 2018. This bill defines hemp as the cannabis plant, any part of it including extracts and cannabinoids with a THC concentration of less than 0.3% dry weight. “Hemp” was removed from the controlled substance act under federal law and is federally not considered a controlled substance [95, 96].
Especially problematic is the purity of the content that can be purchased currently. The requirements for quality control as well as labeling vary significantly from state to state. For example, California requires laboratory testing for medical and recreational cannabis and cannabis products while other states, for example, Arizona, do not mandate any laboratory testing [97, 98].
Over the last several years, including 2019, the FDA has issued several warning letters about unapproved new drugs on the market that allegedly contain CBD. The FDA had tested the content of these products and found a discrepancy of the claimed ingredients on the label and the actual content. Ninety percent of the tested CBD products contained much less CBD that what was posted on the label or no CBD at all, but the majority of tested products did contain a greater content of THC than claimed [99-103].
The FDA explicitly writes on their webpage that these products are not FDA approved for the diagnosis, cure, mitigation, treatment, or prevention of any disease and warns customers to beware purchasing or using any such products [37, 38].
The FDA further states that no food products can enter inter-state commerce and that CBD is not a safe food additive. CBD and other CBD or cannabis derived products should not be considered as dietary supplements as they contain pharmacologically active ingredients. Also, the FDA warns about the various dosing contents as there have been potentially toxic doses reported in certain food, for example, gummi bears containing 1,500 mg of CBD [37, 38].
The interest in cannabis products and CBD has exploded nationally over the last decade and the current trend is to legalize marijuana and make CBD available without strict regulations or control to the general public. CBD can nowadays be purchased online, in natural food stores, pet stores or retail outlet without a physician prescription despite claims for use in medical conditions.
Cannabis and CBD are almost seen as a “wonder drug” in the eye of the general public and claimed to help with conditions that are difficult to treat with established medications: AIDS, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington’s disease and might also mirror some mistrust and frustration in the medications that are currently available as FDA approved medications.
In the case of OUD treatment, people might try to use CBD to avoid being associated with the stigma of treatment for OUD. Buprenorphine and methadone clinics are still seen with some degree of negative stigma even amongst physicians. Affected people try to self-treat with other substances and consult blogs on the internet rather than professional treatment. There are also cases reported of CBD use for other use disorder for example alcohol or tobacco. The use of CBD in these cases bears the risk of potentially developing a new addiction or dependence in the process of substituting one drug with another. Data from Colorado since legalization are alarming and pointing to an increase of opioid use since the increased use of CBs and since legalization of marijuana. Well-established treatments for OUDs are available and should be preferred and advertised.
CBD might have some medicinal value, but main problem is that there is little established research nor control or regulation over the CBD product and people do not know what they are getting when they purchase CBD. CBD products vary highly in compositions and concentrations even from one unit to the other. The FDA issued warning letters about CBD products being falsely labeled and distributed.
The THC content is legally limited to be less than 0.3% but the reality shows that CBD products often contain higher amounts of THC and therefore the user gets put at risk to experience all the toxic side effects that are associated with marijuana and THC. The list of those toxic side effects includes attention-deficit/hyperactivity disorder (ADHD) like symptoms, cognitive impairment, aggression, behavior changes, paranoia, depression, anxiety, cancers and more.
The studies looking at the clinical effect of CBD on certain psychiatric and medical conditions utilize pure forms of CBD that had prior been tested of its contents for its ingredients and concentration, but this is not the form that the general public purchases in a convenience store.
The only form that is FDA approved CBD product that is considered a medication is the Epidiolex. The difference in calling it a “medication” is that one unit is consistent with the next and that it contains always the same dose. For OTC CBD this is not the case, the content varies as well as the psychoactive effect.
Given the inconsistency in the OTC CBD product, there are no dosing recommendations available for each claimed condition and they are not prescribed like a FDA approved medication and there is no physician follow-up.
Also, the use of CBD bears a risk for the user to develop toxic side effects from other medications that they are taking as prescribed as those might develop higher serum concentrations through the interaction of CBD with several CYP P 450 enzymes.
Persons with organ transplants are at risk of increased toxic effects from their immunosuppressant which might lead to organ failure, toxic levels of anticoagulants might lead to acute bleeding, and someone who is prescribed suboxone might experience sedation or respiratory depression even though he/she was previously on a stable dose.
After reviewing the literature, CBD is claimed as a psychoactive substance with effects on mood and behaviors and therefore bears the risk to develop an addiction.
Long-term studies in larger patient cohorts are needed to investigate the addictive potential of CBD.
More studies need to be done in humans in a controlled setting to determine the medicinal value of CBD for various diagnoses in order to be able to make clear recommendations.
Preclinical studies have shown some promising data regarding the medicinal value of CBD but studies in human are not consistent in outcome and controversial in their design. More studies need to be performed in human with larger sample sizes and longer follow-up periods.
Dosing guidelines for CBD need to be established for different indications and follow-up with a physician. The current situation, where the user does not know what they are actually getting in the product, makes CBD unsafe and the risk outweighs the benefit of recommending or using that substance. Especially the content of CBD needs to be under stricter regulations with lab monitoring to determine and guarantee a particular dose or content or CBD and to exclude a higher content of THC than the 0.3% that are allowed by law. Currently there is no consistency in the content of the CBD product.
It is dangerous to assume that the CBD is a “miracle drug” without any safety concerns given the list of potential toxic reactions. Particularly the sedating effect appears to be concerning and limiting in its use.
Cross-interactions with other medications need to be investigated to rule out toxicity in co-morbid patients taken numerous prescribed medications.
A possible development of an addictive disorder to CBD can from the current knowledge not be excluded and further data on long-term administration, the effects of tolerance and toxicity with administration of higher doses need to be investigated. From experience, if a substance is used over a prolonged period of time, there is a process of habituation involved and consecutively an increase in consumption of the substance.
Also, the claimed absence of psycho-active effects and absence of withdrawal symptoms upon discontinuation of CBD is from current point of view, subject to speculation.
The current trend of decriminalization of marijuana and its products bear the risk to further increase the CBD consumption with associated increase in health problems, violence, criminality and lethality.
Nowadays, more people realize good mental health is as important as physical health. Just like you need a healthy body to perform daily tasks, you also need a healthy brain to get through the day.
Our lives are going at a fast pace and leave little to no leisure time. This leads to most people failing to manage their time to look after themselves. The stress from work, family, and relationships can take a toll on your mental health, thus inducing anxiety.
When ignored for a long time, anxiety can affect your mental and physical health. With very little time to spare for self-care, most people resort to cbd oil to relieve anxiety and panic.
Cannabidiol, also commonly known as CBD, is one of the most abundant components found in the Cannabis Sativa plant. The CBD used to make oils, edible flowers, vape cart oils, gummies, etc., is derived from a cannabis plant called hemp. The hemp plant has an insignificant amount of THC; therefore, it does not cause the usual high or pose threats of overdose.
Most people prefer CBD oils for anxiety, PTSD, panic, social anxiety, etc. CBD helps calm the severity of these issues and gives you a calming effect. The research has shown no evidence of the detrimental impact of CBD on your health; therefore, you can use these oils without putting your health at risk.
The most applaudable feature of CBD oils is their versatility. You can either consume the oil as-is, or you can mix it with your food and beverages. Moreover, you can also apply the oil directly to your skin for an instant rejuvenating and anxiety-free experience.
Top 5 CBD Oils & Tinctures for Anxiety: 2022 Review
- Exhale Wellness: Overall Best CBD Oil On The Market, Top Rated
- BudPop: Best CBD Oil for Anxiety
- Hollyweed CBD: Full-Spectrum CBD Oil for Anxiety
- Cheef Botanicals: Strongest CBD Potency
- FAB CBD: Best Value Hemp Oil for Beginners
#1. Exhale Wellness: Overall Best CBD Oil On The Market, Top Rated
Due to its high-quality hemp products, Exhale Wellness has become a popular name in the hemp market. The brand believes that everyone has a right to sound health and a balanced lifestyle.
Situated in L.A., California, Exhale Wellness was founded by passionate researchers who set out to find an alternative method to traditional medicine. With an experience of decades in the food industry, the researchers stumbled upon the idea of using hemp to improve health.
Ever since its inception, Exhale Wellness has succeeded in providing high-quality hemp products at a budget-friendly price. The company aims to bring new and improved products to the market.
With this goal in mind, Exhale Wellness combines the healing properties of hemp with nutritional components to create healthy products. The company manufactures hemp-derived products such as gummies, oils, vape carts, hemp flowers, etc.
Exhale Wellness puts the well-being of its customers above everything. Therefore, every hemp product is a result of thorough research and safe practices. However, Exhale Wellness CBD oils are taking over the hemp market.
Sourcing and Manufacturing: People love the brand because the manufacturers do not compromise the standard of the products. Exhale Wellness manufactures CBD oils with 100% natural and organically sourced hemp. The researchers and cultivators have collaborated with the farmers of Colorado to obtain the highest quality hemp.
CO2 Extraction: The manufacturers use the CO2 extraction technique to extract pure and safe hemp distillate. This technique ensures the quality of CBD oils and is also eco-friendly. The CO2 produced is reused in the process; therefore, this technique does not contribute to the emission of greenhouse gases.
Third-Party Lab Tests: To further ensure the quality, Exhale Wellness subjects all of its products to third-party lab tests. The results are available on the website, and you can access them to verify the purity of products before purchasing it.
Natural and Organic Ingredients: Exhale Wellness uses 100% natural and organic materials in its products. The CBD oils are non-GMO, non-dairy, and gluten-free. Moreover, these products do not contain harmful chemicals and artificial additives that might pose a threat to your health.
Variety: Exhale Wellness’ CBD oils come in two potencies — 600mg and 1,200mg. The oil container is a glass dropper bottle, making it easy to squeeze out a drop or two. This helps prevent the wastage of the product.
- 20% discount on first order
- Third-party lab tested with COAs available
- 30-day money-back guarantee
- Full-spectrum CBD oil
- Only available online
#2. BudPop: Best CBD Oil for Anxiety
BudPop has recently joined the hemp market, but it has proved to be one of the best brands for CBD products. The company was established in 2021 by a group of young researchers and cultivators. The founders believe that natural alternatives to traditional medicine are the best way to get rid of anxiety and live a stress-free life.
Like all of the other well-reputed CBD brands in the market, BudPop cares deeply about the well-being of its customers. Therefore, it does not compromise the quality and standard of its products.
The brand aims to provide safe and secure hemp-derived products to as many people as possible. For that reason, the founders work tirelessly to exceed the customers’ expectations.
The brand’s dedication and commitment towards the cause show that it has the potential to best its competitors. The BudPop team has a collective experience of 30 years in the organic food industry. So, you can consume these products with the confidence that your health is in safe hands.
Recently, BudPop’s CBD oils are creating a lot of hype in the market due to their high potency and palatable taste.
Manufacturing Practices: BudPop sources all of its hemp from the ethically grown hemp plants in the farms of Nevada. To ensure the safety and purity of BudPop products, the manufacturers observe every process from sourcing to packaging.
The manufacturing practices implemented for hemp extraction are sustainable and environmentally-friendly. Additionally, the brand conforms to all of the laws and legalities implemented by the hemp market and agricultural industries.
Independent Lab Tests: The CBD oils distributed by BudPop are non-GMO and free of chemical additives and toxins. Moreover, the brand subjects all of its products to third-party lab tests, and the results are available on the website.
In addition, the brands provide cannabinoid profiles of the products, so you know what you are consuming. This level of transparency shows that the brand is reliable and cares about your health.
Federal Farm Bill Compliant: All BudPop products are Federal Farm Bill compliant. This bill was passed in 2018, and it restricts the hemp brands to use more than 0.3% THC in their products.
Variety: BudPop’s CBD oils come in two different flavors — Peppermint and Natural. Both of these tinctures have calming effects and help regulate the digestive system’s functioning.
The users have reported that these tinctures also treat anxiety and PTSD (Post Traumatic Stress Disorder). Each glass dropper bottle comes with 1,500mg total of CBD.
- Vegan-friendly products
- 30-day money-back guarantee
- Sustainable manufacturing practices
- Free shipping on all orders
- 20% off on first order
- Only available on the brand’s official website
#3. Hollyweed CBD: Full-Spectrum CBD Oil for Anxiety
The most applaudable feature about Hollyweed CBD that makes it one of the top CBD oil brands is their commitment to improvement. The team consists of researchers and scientists with decades’ worth of experience in the cannabinoid industry.
Hollyweed CBD believes in well-being and wholeness for everyone via organic and natural means. The team decided to lay down the foundation after realizing the inconsistency in the hemp market.
Most brands are not honest and transparent with their customers, nor do they care about the effectiveness and purity of the products. The realization led to the idea of creating a brand that puts the health of its customers above everything else.
Thus, the company was started with a goal to make high-quality CBD products accessible to everyone in need. The team behind Hollyweed is a staunch believer of the wholeness in individuals via six pillars of wellness. These pillars are physical, spiritual, emotional, intellectual, social, and environmental.
Since its establishment, Hollyweed CBD has gone out of its way to ensure the customers are satisfied with the quality and potency of the products. And the company has managed to exceed the expectations of its customers, setting the bar too high for competitors.
Zach ‘Jesushands’ Fernandez, a well-known multimedia artist, is a prominent team member. He is a strong advocate of plants and is known for changing the “Hollywood” sign to “Hollyweed” in 2017.
Purity of Products: Hollyweed CBD is completely transparent and honest about its manufacturing practices and ingredients. To ensure the quality, Hollyweed uses organically sourced hemp plants grown on the farms of the U.S.
Hollyweed CBD oils are non-GMO and free of chemical toxins and additives. Moreover, the manufacturers use the CO2 extraction method. This sustainable technique provides the purest hemp extracts and prevents the emission of greenhouse gases.
Transparency: Third-party lab tests then verify the products, and the results are displayed publicly on the website. This shows that the company is trustworthy, and you can rely on it for all of your CBD needs.
Superfood: Hollyweed CBD oil tinctures are a nutrient-rich superfood for your body. These oils are fortified with Omega 3 and 6. Moreover, they contain surplus amounts of fatty acids that help you have a balanced diet. These oils are also a complete source of protein for vegans.
Potency: Hollyweed CBD oils are available in four different potencies — 300mg, 600mg, 1,200mg, and 3,000mg — so you have numerous strength options to choose from.
- Natural and organic ingredients
- Free shipping
- 25% off on first order
- Quiz available to help you choose the right product
- Requires a little longer to take effect
#4. Cheef Botanicals: Strongest CBD Potency
Cheef Botanicals is a popular name in the hemp industry due to its natural and effective CBD products. Being in the market for 25 years, Cheef Botanicals has excelled in the art of distributing safe and healthy hemp-derived products.
Years of dedication and honest policies have earned Cheef Botanicals the trust of millions of customers. A then-young group of entrepreneurs established the brand to educate people about the health benefits of hemp.
The main thing that led to the establishment of Cheef Botanicals was the realization that people have no knowledge of the healing properties of hemp. Therefore, the company aimed to familiarize the people with the detrimental effects of the long-term use of traditional medicine.
To provide the uncompromised and highest-quality products to the customers, Cheef Botanicals collaborated with the professional farmers of Colorado. All of the products manufactured by Cheef Botanicals are safe to use.
Cheef Botanicals’ CBD oils are recently making rounds in the market as one of the best products for relieving anxiety. These oils are full-spectrum, which means they contain less THC and more CBD.
Moreover, these oils also have all of the natural flavonoids, terpenes, and cannabinoids found in hemp plants. So, you can get all of the benefits of CBD without worrying about the usual high that hinders the functioning of your brain.
Manufacturing: The company uses safe and organic hemp grown in the farms of Colorado. The researchers and cultivators monitor the entire process from sourcing to packaging.
Manufacturers use the CO2 extraction method to obtain the purest and safest hemp distillate for CBD oils. This is also environmentally-friendly, so you can consume Cheef Botanicals’ products with a crystal-clear conscience.
Full-Spectrum CBD Oils: Cheef Botanicals’ full-spectrum CBD oils come in four potencies — 300mg, 600mg, 1,200mg, and 3,000mg — and each glass bottle contains 15ml of oil. You can also purchase these in value packs to save money. The oils contain hemp seed oil, which helps customers have a pure, enhanced, and anxiety-free experience.
Purity: Cheef Botanicals’ CBD oils are non-GMO, non-dairy, and gluten-free. Moreover, these oils go through tests, experiments, and research to ensure the products contain no artificial flavors, dyes, or chemical toxins.
These products are also made with vegan-friendly ingredients, making them safe for vegans and health-conscious folks.
Third-Party Lab Tests: Cheef Botanicals’ CBD oils are tested for safety by third-party labs. The results are available on the website, and you can easily access them.
In addition to this, the company displays the cannabinoid profiles of the products on its website. This gives customers a clear idea of how much CBD they are consuming with the product.
- Full-spectrum CBD oils
- 30-day money-back guarantee
- Federal Farm Bill compliant
- 100% organic ingredients
- Free shipping
- Shipping only within the U.S.
#5. FAB CBD: Best Value Hemp Oil for Beginners
Established in Tampa in 2005, FAB CBD aims to bring the best-quality products to the hemp market. Since then, the brand has been on a mission to provide fitness and well-being to more and more people via alternatives to traditional medicine.
FAB CBD consists of a team of professional cultivators who put a lot of effort into bringing the best CBD products to your table. FAB CBD is known for the quality of its products, which shows that only the highest-quality ingredients are used. However, FAB CBD products still fall in the affordable range.
This shows that this brand cares about your health and wants you to have a healthy life within a budget. Such gestures show the sincerity and honesty of the brand.
Although the brand has been in the market for a long time, people have recently increased the demand for its CBD oil. Most users claim it is the best CBD oil for relieving anxiety. Just a few drops may help you forget about the stress and calm your anxiety, giving you a refreshing feeling.
FAB CBD oils are available in five amazing flavors — Berry, Vanilla, Citrus, Mint, and Natural. You also get a range of choices when it comes to potency. The oils come in four strengths — 300mg, 600mg, 1,200mg, and 2,400mg.
Sourcing: FAB CBD’s oils are made with 100% organically sourced hemp plants grown on the farms of Colorado. Moreover, these oils are non-GMO and gluten-free, so vegans can consume them without a doubt.
Manufacturing: The FAB CBD team invests a great deal of time into the manufacturing process and thoroughly studies every step. The company aims to come up with improved and innovative techniques for the extraction of hemp. The manufacturers then use the CO2 extraction method to obtain the highest-quality pure CBD distillate. This technique does not leave solvents in the distillate; therefore, it is free of toxins and chemicals.
Independent Lab Testing: To further ensure the safety of the products, FAB CBD sends all of its products for third-party lab testing. The labs check whether the companies comply with the hemp industries and agricultural sector regulation.
The results of the tests are available on the company’s website, and you can access them to verify the authenticity of the products.
Authenticity: FAB CBD’s products pass the authenticity test as well. The company’s website mentions all of the products are Federal Farm Bill compliant.
This means FAB CBD’s oils are made with a minimum THC, i.e., less than 0.3%. Therefore these products do not alter your thinking or respiratory capabilities like common psychoactive drugs.
- Royalty program for regular users
- “Most dependable” according to users
- Simple and convenient user interface
- 30-day money-back guarantee
- International shipping takes time
How We Chose These Brands
Making up your mind regarding a single CBD oil can be difficult, especially when you have multiple options to choose from.
When you start comparing the pros and cons of different products, every brand seems to have similar things to offer. For someone with anxiety, picking one brand out of a pile of hundreds only adds to the stress.
Therefore, we researched the best CBD oil brands and narrowed down the list. We generated a list of some of the important factors that determine the worth of a brand.
We carefully checked all brands against those metrics and kept cutting the names off our list. In the end, we chose the best five CBD oil brands that are a great help for anxiety.
What We Looked For
We considered the following metrics to determine whether the brands we chose are worth your time and money or not.
The foremost thing that gives away the quality of a brand is its reputation in the market. That is the sole reason high-quality brands work hard to maintain the standard and their name in the market. Therefore, we preferred the brand with a good reputation.
Honesty and Transparency
The brands that follow the standards set by the hemp industries have nothing to hide. Thus, we looked at different brands’ policies and techniques before making up our minds. In the end, we stuck with the brand that did not hesitate in providing us with all of the information we needed.
Price is a very important factor in determining the worthiness of a brand, as most attract customers with low prices. This, however, can imply that the brand uses substandard ingredients to save the manufacturing cost. Therefore, we invested a lot of time researching the brands that sell the highest-quality CBD oils at an affordable price.
Customer reviews are the most important factor in forming an image of the company. A brand might get a reputable name in the market using carefully crafted strategies, but it does not last long. The reviews from customers paint an honest picture of the quality of the products offered by the brand.
Hence, we only kept the brands with maximum positive reviews from the customers across a variety of platforms. This helped us get a clear idea about the brands and their services.
Buying Guide for Beginners
With the explosive rise in the popularity of CBD oils, CBD brands have started popping everywhere. While this is a good thing, considering the increasing demand for CBD products, it does have its disadvantages.
Most brands make use of such a situation to make some money. Whether you are a first-timer or a regular CBD user, determining which brand cares about the well-being of its customers is not an easy job.
However, you can save yourself the scrutiny of combing through hundreds of products by considering crucial factors. The following list entails some key factors that you must consider before spending money on CBD oils.
Safe and Pure Ingredients
Before buying a product, you should always take a look at the ingredients used by the companies. Most high-quality manufacturers use non-GMO, gluten-free ingredients that are also free of additives, artificial colors, or flavors.
Sometimes, brands add extra ingredients for an enhanced effect. Although these might not be harmful to most, they could set off an allergic reaction if you are sensitive. Therefore, it is better to always read the ingredients column of the products before making up your mind.
Always check the brand’s authenticity to avoid falling prey to scams. The authenticity of a brand can be tested by looking up the third-party lab results and the Certificates of Analysis (COAs). Both of these can be found on the company’s website, and if not, you are better off without that brand.
Reading customer reviews across a variety of platforms can also help you evaluate the authenticity of CBD oil brands.
Sourcing of Hemp
Most companies use organically grown hemp from the farms of Colorado and Nevada. Meanwhile, some companies grow their hemp under controlled conditions and artificial light. Additionally, hemp plants tend to absorb most of the chemicals they are exposed to while growing, and these compounds can make their way to the CBD oils.
Some companies use substandard hemp plants to produce CBD products. But, these products can prove to be harmful in the long run. Additionally, hemp sourced from overseas can contain harmful additives that are used in the transportation process, and these additives can have a negative impact on your health. Therefore, you should check the hemp sources of the company before purchasing its products.
Most extraction techniques use harmful chemicals to extract CBD from hemp plants. Sometimes, the residues of these chemicals are left behind and become a part of the product during manufacturing. Even after refining products, some of the stubborn chemicals refuse to leave.
These chemicals can seriously affect your health if used for a long time. Therefore, high-quality CBD manufacturers use safe and sustainable extraction techniques to maintain the cleanliness and effectiveness of the product.
The most common of these is the CO2 extraction technique. It obtains the purest extract from hemp plants leaving behind zero chemical residues. Moreover, it is eco-friendly to reuse the CO2, preventing its emission into the environment.
Therefore, always run a background check to see which extraction techniques the company employs. If you do not find a satisfactory answer, it is better not to waste money on those brands.
FAQ: CBD Oil
Q1. How do cannabinoids work?
Cannabinoids are essential for a cell-signaling system of human bodies called the Endocannabinoid System (ECS). The cells of the ECS contain cannabinoid receptors on their walls. These receptors bind with cannabinoids, and the enzymes break them down to regulate the functioning of the brain, like preventing stress, anxiety, PTSD, etc. A healthy ECS can produce and distribute enough cannabinoids to maintain optimal functioning. However, stress, exhaustion, and poor diet can lead to an imbalance in the ECS.
Therefore, CBD oils are an excellent way to boost the low cannabinoid number in ECS to resume normal brain functioning. The external CBD sources replenish the body with cannabinoids and aid the ECS.
Q2. What is a full-spectrum CBD oil?
Full-spectrum CBD oils contain all of the extracts of the hemp plant. These include essential oils, terpenes, flavonoids, CBD, and other cannabinoids. The legally grown hemp plants have the minimum amount of THC, i.e., less than 0.3%, which is considered a trace amount.
The reason is that this amount is not significant enough to cause the effects of common psychoactive drugs; therefore, it is safe for consumption.
Q3. Do CBD oils for anxiety have side effects?
Generally, all of the research around CBD has proven that it has no long-term side effects and is safe for consumption. However, first-timers might experience inconveniences such as diarrhea, nausea, fatigue, and red eyes.
These side effects are not long-lasting and go away after some time. With time, your body gets used to CBD, develops immunity to these side effects, and you do not feel anything.
Also, the CBD may react with your prescription medications; therefore, it is better to consult your doctor before starting CBD oils.
With the explosive increase in the usage of CBD oils to help lessen generalized anxiety disorder and panic, the demand has heightened. Therefore, multiple brands have arisen to fill the gap between supply and demand. However, not all of these brands live up to the customers’ expectations. This can be more problematic if you are a beginner, as finding brands that cater to your specific needs is not easy.
Therefore, we made a list of the top five brands that provide the highest-quality CBD oils. These companies use U.S.-grown hemp and sustainable and safe manufacturing techniques to produce safe and organic CBD oils.
Moreover, these companies put their customers before their business and provide excellent customer services. They get their CBD oil products tested from third-party labs and display the results on their websites.
If you are looking for instant and convenient relief from anxiety disorders without spending a lot of money, we suggest you try these brands. We affirm you will not regret trying at least one of these brands out.
The news and editorial staff of the Bay Area News Group had no role in this post’s preparation.