CBD (Cannabidiol): Benefits, Forms, Dosing, and Side Effects

Table of Contents

• Overview
• Forms and Bioavailability
• Evidence for Benefits
• Recommended Dosing
• Safety and Side Effects
• Drug Interactions
• Dietary Sources
• References

Overview

Cannabidiol (CBD) is one of over 100 cannabinoid compounds found in the Cannabis sativa plant [1][2]. Unlike tetrahydrocannabinol (THC) — the primary psychoactive cannabinoid responsible for marijuana's intoxicating effects — CBD is not believed to produce psychoactive effects affecting perception and behavior [1][3]. The cannabis plant contains approximately 540 chemical substances, with CBD and THC being the two dominant cannabinoids [2].

CBD exists naturally in the plant primarily as cannabidiolic acid (CBDa), its precursor compound, which converts to CBD through decarboxylation (heat or aging). When CBDa converts to CBD, the conversion is efficient: 87.7% of CBDa in a product can be counted as CBD [1]. This distinction matters when reading supplement labels, as some products list CBDa content rather than CBD content.

Another non-psychoactive cannabinoid gaining attention is cannabigerol (CBG), along with its precursor cannabigerolic acid (CBGA). Laboratory research suggests CBG may share some effects with CBD, with CBG potentially having stronger anti-inflammatory effects but less potent pain-relieving effects [4][5]. However, no clinical studies in humans have confirmed health benefits of CBG. People have reported using CBG-predominant products for anxiety, chronic pain, depression, insomnia, and migraine [6].

CBD products also contain terpene compounds — aromatic molecules found in fruits and vegetables (such as the citrus-scented terpene limonene). An "entourage effect" (synergistic interaction between cannabinoids and terpenes) has been proposed, but it remains unclear whether or how terpenes meaningfully impact CBD's effects [1].

The legal landscape for CBD is complex. The FDA has not approved the cannabis plant for any medical use, but has approved several cannabinoid-based drugs [2]:

• Epidiolex — purified CBD derived from cannabis, approved for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex
• Marinol and Syndros — containing dronabinol (synthetic THC), approved for chemotherapy-induced nausea/vomiting and HIV/AIDS-related appetite loss
• Cesamet — containing nabilone (a synthetic THC analogue), approved for chemotherapy-induced nausea/vomiting

The FDA has determined that products containing THC or CBD cannot legally be sold as dietary supplements, and foods with added THC or CBD cannot be sold in interstate commerce [2]. State laws vary regarding intrastate sales.

Forms and Bioavailability

Types of CBD Products

CBD is available in multiple forms, each with distinct characteristics:

Form	Description	Typical CBD Content
Full-spectrum hemp extract	Contains CBD plus other cannabinoids (including trace THC <0.3%), terpenes, and flavonoids	Varies; check label for CBD per serving
Broad-spectrum hemp extract	Similar to full-spectrum but with THC removed	Varies; check label for CBD per serving
CBD isolate	Purified CBD (typically 99%+) with no other cannabinoids	Precisely measurable
Hemp oil / Hemp seed oil	Oil from hemp seeds; contains minimal to no CBD	Little to no CBD

An important distinction: "hemp oil" alone would not be expected to contain meaningful CBD, whereas "hemp extract" or products specifically listing CBD as an ingredient should contain CBD [1]. If a product lists only "cannabinoids" without specifying CBD content, the actual CBD amount is unknown.

Oral Bioavailability

CBD is highly lipophilic (fat-soluble), and oral bioavailability without food may be as low as 6% [7]. Taking CBD with a fat-containing meal dramatically improves absorption:

• A 5-fold increase in blood levels of CBD occurred when an oral CBD solution was taken with a high-fat/high-calorie meal versus on an empty stomach [7][8]
• Another study found a 4-fold increase in blood levels when 200-300 mg of purified CBD extract in capsules was taken with a high-fat meal (500-600 calories from fat) compared to fasting. Blood levels temporarily reached a peak 14 times higher, and the half-life extended from 24 hours to 39 hours with food [9]

After oral administration, peak blood levels of CBD are typically reached within 2.5-5 hours. The half-life of CBD in the blood ranges from 18-32 hours under normal conditions [7] to 56-61 hours after 7 days of repeated high dosing [8].

Enhanced Absorption Formulations

Several delivery technologies aim to improve CBD absorption:

• VESIsorb (nano-colloid): A company-funded study found that a 25 mg dose of CBD formulated with VESIsorb increased blood levels 2.9 times compared to the same extract in oil when taken on an empty stomach — though this increase was less than what is achieved simply by taking CBD with a fat-containing meal [10]
• Liposomal formulations: A liposomal CBD preparation using sunflower lecithin (phosphatidylcholine) increased bioavailability of a 10 mg dose by 17-fold one hour after consumption compared to unformulated CBD taken on an empty stomach. CBD was undetectable in 2 of 5 volunteers who took the unformulated version [11]

Transdermal and Topical Delivery

CBD appears to be better absorbed through the skin than THC [12]. Topical CBD preparations (creams, gels, lotions) deliver CBD locally rather than systemically. A study of transdermal CBD gel for epilepsy (195 mg or 390 mg twice daily for 12 weeks) raised blood levels comparable to oral administration, but did not reduce seizures compared to placebo [13].

Does CBD Convert to THC in the Body?

Although some preliminary laboratory studies suggested CBD might convert to THC during digestion [14], a clinical trial showed that no THC was detected in blood up to 6 hours after consuming 300 mg of pure CBD (99.5%), with or without food. None of the participants experienced psychoactive effects associated with THC [15].

Evidence for Benefits

Epilepsy and Seizure Disorders

This is the most well-established medical application of CBD, supported by the FDA approval of Epidiolex.

Dravet syndrome: A placebo-controlled clinical trial found that a high daily dose of CBD (20 mg/kg body weight — hundreds of milligrams) reduced the frequency of convulsions in children and young adults with this rare, severe form of epilepsy. However, CBD was also associated with higher rates of adverse effects including diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal liver function tests (Devinsky et al., N Engl J Med, 2017) [16].

Lennox-Gastaut syndrome: The same high daily dose (20 mg/kg) reduced drop seizures in a 3-month study of treatment-resistant Lennox-Gastaut syndrome. Seizures per month decreased 44% with CBD versus 22% with placebo. Adverse effects again included diarrhea, somnolence, fever, decreased appetite, and vomiting (Thiele et al., Lancet, 2018) [17].

Both studies were funded by GW Pharmaceuticals, the maker of Epidiolex. Notably, the UK's National Institute for Health and Care Excellence (NICE) initially raised concerns about these trials, particularly their short duration, because other antiepileptic drugs are known to lose effectiveness over time (Dijk, BMJ, 2019) [18].

Refractory epilepsy in children (commercially available CBD): A study of 108 children with refractory epilepsy treated with commercially marketed CBD preparations found CBD comparable to the anticonvulsant clobazam as add-on therapy. A seizure reduction of at least 50% occurred in 33% receiving CBD, 38% receiving clobazam, and 44% receiving both. Notably, CBD appeared to increase alertness and verbal interactions compared to clobazam, without the sedation common with clobazam. The average daily dose was approximately 3 mg/kg body weight (e.g., 100 mg/day for a 73 lb child) (Porcari et al., Epilepsy Behav, 2018) [19].

Focal epilepsy (transdermal CBD): A study in Australia and New Zealand giving high-dose transdermal CBD gel (195 mg or 390 mg twice daily) for 12 weeks to 174 adults with focal epilepsy (the most common form) did not show a reduction in seizure activity compared to placebo, despite achieving adequate blood levels of CBD (O'Brien et al., JAMA Netw Open, 2022) [13].

Synthesis: CBD is effective for reducing seizures in rare, severe epilepsy syndromes (Dravet, Lennox-Gastaut) at high doses (20 mg/kg/day), but evidence does not support its use for more common forms of epilepsy [2][16][17].

Anxiety

Several small studies suggest CBD may reduce anxiety, particularly in social and performance-related contexts, although the evidence involves varying doses with inconsistent results.

Social anxiety — public speaking: A placebo-controlled study found that a single 300 mg dose of CBD given 90 minutes before a simulated public speaking test reduced anxiety in treatment-naive patients with social anxiety disorder. A lower dose (150 mg) was not effective, and results with 600 mg were mixed (Bergamaschi et al., Neuropsychopharmacology, 2011; Zuardi et al., J Psychopharmacol, 1993; Linares et al., Braz J Psychiatr, 2018) [20][21][22].

General anxiety — single dose: A placebo-controlled study found that a single 400 mg dose of CBD taken as a capsule reduced self-reported anxiety in healthy young men one hour after ingestion, though it also increased feelings of mental sedation (Crippa et al., Neuropsychopharmacology, 2004) [23].

Social anxiety in adolescents: A study among Japanese teenagers with social anxiety found that 300 mg of CBD (in MCT oil, no THC) daily for 4 weeks led to a modest decrease in symptoms compared to placebo (olive oil) (Masataka, Front Psychol, 2019) [24].

Chronic worriers: A study of 63 adults who tend to be worriers found that 125 mg of CBD twice daily for 2 weeks modestly reduced symptoms of anxiety (trembling, rapid breathing) compared to placebo, but did not reduce worry severity. Lower doses (25 mg twice daily), a single high dose (300 mg), and a single lower dose (50 mg) were all ineffective for both worry and anxiety (Gournay et al., Psychopharmacology, 2023) [25].

Clinical case series: In a group of 72 patients treated with CBD daily for 2 months at an outpatient mental health clinic in Colorado, anxiety scores decreased within the first month in 79.2% of patients and remained decreased throughout the study. Most took 25 mg of CBD daily and continued their prescribed medications. However, 15.3% reported worsening anxiety. CBD was taken after breakfast for anxiety (Shannon et al., Perm J, 2019) [26].

No benefit in healthy adults at low doses: A study of 102 healthy young adults found that drinking a beverage containing about 30 or 60 mg of CBD (plus 177 mg of L-theanine) daily for 8 weeks did not significantly reduce symptoms of anxiety or depression compared to placebo (Ramani et al., BBI — Integrative, 2024) [27].

Healthcare workers during COVID-19: A study gave 118 healthcare workers high-dose CBD (150 mg twice daily) for 28 days. The CBD group had a slightly greater reduction in anxiety symptoms (30% decrease vs 2%) compared to standard care alone, but results for burnout were not statistically significant. Four participants developed elevated liver enzymes, including one severe case (Crippa et al., JAMA Netw Open, 2021) [28].

Synthesis: CBD at doses of 125-600 mg may reduce acute anxiety, particularly in social/performance settings. The 300 mg single dose has the most consistent evidence for social anxiety. Lower doses (15-60 mg) appear ineffective. Effects on chronic, generalized anxiety are less clear [1][20][25][26].

PTSD

Preliminary evidence from case reports suggests CBD may help relieve PTSD symptoms.

A series of case reports from a Colorado clinic found that in 11 adults with diagnosed PTSD, overall symptoms decreased by an average of 28% over 2 months of CBD supplementation. The average daily dose was 33.4 mg at the start, increasing to 44.6 mg by the end of the study. Participants took 25 mg capsules and/or an oral spray (1.5 mg CBD per spray) (Elms et al., J Altern Complement Med, 2019) [29].

Separately, CBD was reported helpful for a 10-year-old girl with anxiety and sleep disorder due to PTSD from sexual abuse. She took 25 mg CBD at bedtime and 6-12 mg from sublingual spray as needed during the day for 5 months. Her anxiety and sleep improved to the point that they were no longer classified as disorders (Shannon et al., Perm J, 2016) [30]. However, there is concern that cannabinoids may affect brain development in children.

From the NIH/NCCIH: Observational studies of PTSD patients who chose to use cannabis have not provided clear evidence of benefit or harm, and only one very small study (10 people) found the cannabinoid nabilone more effective than placebo for PTSD-related nightmares (Jetly et al., Psychoneuroendocrinology, 2015) [31][2].

Sleep

CBD's effects on sleep appear to depend on dose, the presence of underlying conditions, and the population studied.

Insomnia: A small study of 15 people with insomnia found that 160 mg of CBD taken 30 minutes before bedtime for one week significantly increased self-reported sleep duration compared to placebo. Ten of 15 participants reported sleeping more than 7 hours with CBD versus 6 of 15 with placebo. However, there was no decrease in time to fall asleep. Lower doses (40 mg and 80 mg) did not increase sleep time (Carlini et al., J Clin Pharmacol, 1981) [32].

Healthy adults — no benefit: A dose of 300 mg CBD taken 30 minutes before bedtime had no effect on time to fall asleep, time spent in sleep stages (including REM), total sleep time (measured by polysomnography), or self-reported sleep quality in healthy men compared to placebo. CBD did not impair cognitive function the following morning (Linares et al., Front Pharmacol, 2018) [33].

Low-dose CBD — no benefit: A study of 65 healthy, overweight adults found that 15 mg of CBD from hemp extract taken daily for 6 weeks did not improve sleep quality, mood, or ability to cope with stress compared to placebo (Lopez et al., J Diet Suppl, 2020) [34].

CBD + melatonin: Taking 15 mg of CBD with 5 mg of melatonin once daily at bedtime for one month did not improve sleep quality compared to taking either supplement alone, though it did not increase side effects or grogginess either (Saleska et al., J Am Nutr Assoc, 2023) [35].

Clinical case series: In the Colorado clinic case series of 72 patients, sleep scores improved within the first month in 66.7% but fluctuated over time. Notably, 25% reported worsening sleep. Most took 25 mg of CBD daily (Shannon et al., Perm J, 2019) [26].

Dose-dependent effects on alertness: Preliminary research suggests CBD may have a stimulating effect at low doses (around 15 mg) while being sedating at moderate to high doses, and may improve sleep primarily in people with anxiety or other conditions rather than in healthy individuals (Babson et al., Curr Psychiatry Rep, 2017) [36].

Synthesis: CBD at 160 mg may increase sleep duration in people with insomnia, but lower doses (15-80 mg) appear ineffective, and CBD does not appear to help healthy people without sleep disorders. The evidence is preliminary and inconsistent [1][26][32][33][34].

Pain

The evidence for CBD as an oral pain reliever is weak. Most positive studies have used combinations of THC and CBD rather than CBD alone. There is some preliminary evidence for topical CBD in specific pain conditions.

Oral CBD for Pain

Acute low back pain: A study of 100 adults treated in an emergency room found that a single high dose of CBD (400 mg in MCT oil) added to standard treatment (acetaminophen + ibuprofen) did not reduce pain better than placebo, did not reduce the need for rescue opioid medication, and did not shorten hospital stays (Bebee et al., Med J Aust, 2021) [37].

Arthritis pain: A 3-month study of 129 adults with moderate chronic pain from hand osteoarthritis or psoriatic arthritis found that CBD (starting at 10 mg, increasing to 20-30 mg daily) did not decrease pain or improve sleep quality, depression, or anxiety compared to placebo (Vela et al., Pain, 2021) [38]. A review of four clinical studies investigating cannabinoids for rheumatic diseases concluded there is "currently insufficient evidence to recommend cannabinoid treatments for management of rheumatic diseases" (Fitzcharles et al., Schmerz, 2016) [39].

Cancer-related pain: High-dose CBD oil (average 400 mg/day) for one month did not reduce self-reported pain, the need for opioid medication, fatigue, nausea, appetite loss, depression, anxiety, or any other quality-of-life measure compared to placebo in 144 adults with advanced cancer. Concerningly, more CBD recipients (8 vs 2) experienced new or worsening shortness of breath (Hardy et al., J Clin Oncol, 2022) [40].

Chronic pain with opioid use (no placebo control): A study gave hemp extract softgels (31.4 mg CBD/day) to 94 patients with chronic pain who had been on opioids for at least one year. Among those who completed the study, 94% reported quality-of-life improvements and 53% reduced their opioid use. However, this study lacked a placebo control and was funded by the hemp extract manufacturer (Capano et al., Postgrad Med, 2019) [41].

Pain perception: A review of experimental pain studies found that cannabis products containing CBD (plus THC) may not reduce pain intensity but may make pain feel less unpleasant. However, a subsequent study found that CBD alone (50 mg) did not reduce pain threshold, tolerance, or severity compared to placebo, and suggested the reduction in pain "unpleasantness" may be largely a placebo effect (De Vita et al., Exp Clin Psychopharmacol, 2021; De Vita et al., JAMA Psychiatry, 2018) [42][43].

Chronic pain (NIH review): A 2018 review of 47 studies (4,743 participants) of cannabis/cannabinoids for chronic non-cancer pain found evidence of only a small benefit: 29% had a 30% pain reduction with cannabis versus 26% with placebo — a difference that may be too small to be meaningful. Adverse events were more common with cannabis/cannabinoids [44]. A 2015 review of 28 studies (2,454 participants) found improvements in pain measures with cannabinoids, but these did not reach statistical significance in most studies [45].

Topical CBD for Pain

Topical preparations show more promise than oral CBD for certain localized pain conditions, though evidence remains preliminary.

Thumb arthritis: A study of 18 adults with basal thumb joint arthritis found that CBD cream (6.2 mg CBD in shea butter) applied twice daily for 2 weeks significantly reduced pain (from 5 to 2 on a 10-point scale vs no decrease with placebo) and disability (39% reduction vs 14%). However, physical tests of thumb function did not improve (Heineman et al., J Hand Surg, 2022) [46].

Temporomandibular disorder (TMD): A study of 60 young adults with jaw muscle pain found that CBD ointment (approximately 7 mg CBD per application) applied twice daily for 14 days reduced pain intensity by 70% versus 10% for the control group. A follow-up study found that intraoral CBD gel (20 mg or 40 mg daily for 30 days) also reduced pain significantly compared to placebo, though application to the skin appeared more effective than inside the mouth (Nitecka-Buchta et al., J Clin Med, 2019; Walczynska-Dragon et al., J Clin Med, 2024) [47][48].

Peripheral neuropathy: A study of 29 adults with peripheral neuropathy found that CBD cream blended with emu oil applied up to 4 times daily for one month modestly reduced self-reported intense pain, sharp pain, cold sensations, and itchiness compared to placebo — but did not reduce hot, dull, sensitive, or deep pain (Xu et al., Curr Pharm Biotechnol, 2019) [49].

No benefit after knee replacement: Topical CBD applied around the knee 3 times daily for 2 weeks after knee replacement surgery did not reduce pain, opioid use, or improve knee function compared to placebo in 80 adults (Haffar et al., J Arthroplasty, 2022) [50].

No benefit for exercise-induced soreness: CBD cream applied after leg exercises did not decrease delayed-onset muscle soreness compared to placebo in 13 young adults (Garcia et al., Int J Exerc Sci, 2019) [51].

Synthesis: Oral CBD does not appear to reduce most types of pain when used without THC. Topical CBD shows preliminary benefit for localized conditions — particularly thumb arthritis, temporomandibular disorder, and peripheral neuropathy — but not for post-surgical pain, exercise-induced soreness, or knee osteoarthritis [1][37][38][40][46][47][49].

Parkinson's Disease and Movement Disorders

CBD does not appear to improve motor symptoms of Parkinson's disease. However, it may help non-motor symptoms such as psychosis, mood disturbances, and sleep disorders [53].

Quality of life: A small double-blind, placebo-controlled study found no motor function improvement in adults with mild-moderate Parkinson's disease taking 75 mg or 300 mg CBD daily for 6 weeks. However, those taking 300 mg CBD had significant improvements in activities of daily living, stigma, and emotional well-being (Chagas et al., J Psychopharmacol, 2014) [54].

REM sleep behavior disorder: In three older men with Parkinson's and RBD, none experienced disruptive sleep episodes during a 6-week period of daily 75 mg CBD dosing. A fourth man taking 300 mg daily reduced episodes from 2-4/week to once/week (Chagas et al., J Clin Pharm Ther, 2014) [55].

Psychosis: Preliminary reports suggest CBD at 150-400 mg may improve psychotic symptoms in Parkinson's patients without worsening motor function (Zuardi et al., J Psychopharmacol, 2009) [56].

Dystonia: A preliminary trial found modest improvements in dystonia symptoms in five individuals taking 100-500 mg/day. However, at the highest dosages, tremor and movement initiation worsened in two participants who also had Parkinson's disease (Consroe et al., Int J Neurosci, 1986) [57].

Essential tremor: A study of 19 people found that a single dose of 300 mg CBD did not reduce upper limb tremor severity compared to placebo (Santos de Alencar et al., Parkinsonism Relat Disord, 2021) [58].

Schizophrenia and Psychosis

Positive trial: A study of high-dose CBD (500 mg morning and evening) in adults with schizophrenia found that adding CBD to existing treatments for 6 weeks reduced psychotic symptoms. CBD was well tolerated (McGuire et al., Am J Psychiatry, 2017) [59].

Negative trial: A 6-week study found that 300 mg CBD twice daily did not improve cognitive or psychotic symptoms in adults with schizophrenia. Twenty percent of CBD recipients experienced sedation versus 5% on placebo (Boggs et al., Psychopharmacology, 2018) [60].

Mechanism — brain imaging: A single 600 mg dose of CBD in people at high risk of psychosis caused brain activity patterns during a verbal learning task to more closely resemble those of people not at risk of psychosis. A possible mechanism is that CBD at 600-800 mg/day elevates natural levels of the endocannabinoid anandamide by moderately inhibiting its degradation (Bhattacharyya et al., JAMA Psychiatry, 2018; Rohleder et al., Front Pharmacol, 2016) [61][62].

Substance Use Disorders

Heroin use disorder: High-dose CBD (400 mg or 800 mg) taken once daily for 3 days reduced drug cravings in a placebo-controlled study of 42 adults with heroin use disorder. Both doses were equally effective. No serious adverse events occurred (Hurd et al., Am J Psychiatry, 2019) [63].

Cannabis use disorder: A 4-week trial of 82 people found that 100 mg CBD twice daily was not effective. However, 200 mg twice daily provided modest benefit — about half a day more abstinence per week than placebo, confirmed by reduced urinary THC metabolite levels (Freeman et al., Lancet Psychiatry, 2020) [64].

Multiple substance use disorder — case report: A 17-year-old male with multiple substance use disorders, depression, and social phobia was started on 100 mg CBD, gradually increased to 600 mg for 8 weeks. He improved in depressive and anxiety symptoms and quit abusing drugs without withdrawal (Laczkovics et al., Neuropsychiatr, 2020) [65].

Gastroparesis

A 4-week placebo-controlled study at the Mayo Clinic found that very high-dose CBD (~750 mg per dose, twice daily) improved symptoms of gastroparesis. Paradoxically, CBD further slowed stomach emptying rather than improving it, leading researchers to speculate benefits came from reduced gut sensation. The only notable side effect was diarrhea (Zheng et al., Clin Gastroenterol Hepatol, 2023) [66].

Multiple Sclerosis

Most MS research has involved THC+CBD combinations (particularly nabiximols/Sativex), not CBD alone. A review of 17 studies (3,161 participants) found a small improvement in patient-assessed spasticity, pain, and bladder problems, but no significant improvement on objective spasticity measures [67]. The American Academy of Neurology concluded in 2014 that nabiximols is probably effective for improving subjective spasticity symptoms [69]. The contribution of CBD independent of THC in these preparations is uncertain [2].

Nausea and Vomiting (Chemotherapy-Related)

A 2015 Cochrane review of 23 studies (1,326 participants) found that the cannabinoids dronabinol and nabilone were more effective than placebo for chemotherapy-induced nausea/vomiting. This research was done primarily in the 1980s-1990s and used synthetic THC analogues, not CBD [70].

Psoriasis

A study of 26 adults with mild plaque psoriasis found that 30 mg CBD orally twice daily for 12 weeks did not improve plaque appearance or decrease itching compared to placebo [71].

Hair Loss

A study of 35 adults with androgenetic alopecia found that applying hemp extract paste containing CBD to bald areas once daily for 6 months substantially increased hair counts — 74.1% increase in temple areas for men and 55.2% for women. However, there was no placebo control. About one-third reported increased hair shedding during the first month (Smith et al., Cannabis, 2021) [72].

Cancer

Preliminary evidence suggests CBD may have anti-cancer properties, but no clinical trials have been conducted. A single case report described a man in his early 80s with lung adenocarcinoma who had a dramatic reduction in tumor size after self-administering low-dose CBD twice daily (Sule-Suso et al., SAGE Open Medical Case Reports, 2019) [73]. This is a single anecdotal case and does not constitute evidence of efficacy.

COVID-19 and Viral Infections

CBD has been promoted for COVID-19, but there is no direct clinical evidence. Laboratory research found that CBD inhibited SARS-CoV-2 replication in cell cultures [74]. However, when high-dose CBD was given to children for seizures, upper respiratory infections were slightly more common in the CBD group (11% vs 8%) [16]. Animal experiments suggest CBD may dampen immune responses, which could theoretically benefit autoimmune conditions but might also worsen infections [75][76].

Glaucoma

CBD does not appear beneficial and may be harmful. A 40 mg dose of CBD temporarily increased intraocular pressure [77]. An animal study also found that CBD applied directly to the eye caused an undesirable pressure increase [2]. Cannabis-based products that do lower intraocular pressure (primarily via THC) only do so briefly and are not as effective as existing treatments [2].

Inflammatory Bowel Disease

A 2018 Cochrane review of 3 studies (93 participants) of cannabis/cannabis oil for active Crohn's disease found no difference in clinical remission [107]. For ulcerative colitis, a 2018 Cochrane review of 2 studies (92 participants) found that CBD capsules did not differ from placebo for remission, and those taking CBD had more side effects [108].

Opioid Use Reduction

A 2017 review of 9 human studies (750 participants), including 3 high-quality RCTs, found inconsistent results — none of the high-quality studies showed that cannabinoids could lead to decreased opioid use [78]. Population-level data has also been inconsistent [79][80].

Recommended Dosing

Most clinical research has used daily doses of hundreds of milligrams of CBD — far more than most commercial products provide (which typically deliver tens of milligrams or less per day). It is not known whether these lower doses are as effective [1].

Doses Used in Clinical Studies

Indication	Daily Dose	Duration	Notes
Social anxiety (acute)	300 mg single dose	One-time	Taken 90 minutes before stressor [20][22]
Generalized anxiety	125 mg twice daily (250 mg total)	2 weeks	Modest benefit for physical anxiety symptoms [25]
Insomnia	160 mg	Nightly	30 min before bedtime; increases sleep duration but not onset latency [32]
Epilepsy (Dravet/LGS)	20 mg/kg/day	Ongoing	FDA-approved as Epidiolex; divided into 2 doses [16][17]
Schizophrenia (adjunctive)	1,000 mg/day	6 weeks	500 mg morning and evening [59]
Heroin craving reduction	400-800 mg/day	3 days	Both doses equally effective [63]
Cannabis use disorder	400 mg/day	4 weeks	200 mg twice daily; 100 mg twice daily ineffective [64]
Parkinson's quality of life	300 mg/day	6 weeks	75 mg not effective for QoL measures [54]
Gastroparesis	~1,500 mg/day	4 weeks	~750 mg twice daily (~10 mg/kg) [66]

Practical Dosing Considerations

Start low and increase gradually. For individuals who wish to try CBD for anxiety or sleep, starting with 25-50 mg daily and increasing as tolerated over several weeks is a conservative approach, though most positive clinical evidence involves doses of 150-300 mg or more [1][26].

Take with fat-containing food. CBD bioavailability is dramatically increased (4-5 fold) when taken with a meal containing fats. Taking CBD on an empty stomach may result in as little as 6% absorption [7][8][9].

Timing: For anxiety, studies have dosed CBD 60-90 minutes before the anxiety-provoking situation [20][23]. For sleep, 160 mg taken 30 minutes before bedtime has been studied [32]. For ongoing conditions, CBD is typically taken in divided doses (morning and evening).

Read labels carefully. Look for products that list the amount of CBD per serving, not just per bottle. "Hemp oil" alone does not provide meaningful CBD. "Full-spectrum" products contain trace THC (<0.3%) and other cannabinoids; "CBD isolate" products contain purified CBD only [1].

Safety and Side Effects

Common Side Effects

At typical supplement doses (tens of milligrams), CBD appears generally well tolerated. An analysis of adverse events reported with PlusCBD products (5 million units sold 2018-2019) found that only 0.03% of sales resulted in a reported adverse event. The most common adverse events with oral use were abdominal discomfort (24% of reports), headache (7%), hypersensitivity (6%), and nausea (6%) [81].

Side Effects at High Doses

Very high daily doses (20 mg/kg/day — hundreds to thousands of milligrams) carry significantly greater risks [1][16][17][82]:

• Gastrointestinal: Decreased appetite, diarrhea, vomiting, nausea
• Neurological: Fatigue, somnolence, sedation
• Hepatic: Elevated liver enzymes (ALT/AST) — occurring in 8% at 10 mg/kg/day and 16% at 20 mg/kg/day [82]
• Hematologic: Approximately 35% of people treated for epilepsy with 10-20 mg/kg/day developed anemia versus 14% on placebo [8]
• Weight loss: At 25 mg/kg/day, adverse events occurred in 80.8% of children. Weight loss was clinically significant in 30.7% [83]

Cardiovascular Effects

A single 600 mg dose of CBD in healthy young men decreased resting systolic blood pressure by 6 mmHg and increased heart rate by approximately 10 bpm [84]. Blood pressure drops of 10-20 mmHg upon standing were reported in patients taking 100-500 mg CBD [57].

Cannabinoid Hyperemesis Syndrome

Rarely, recurrent nausea, vomiting, and abdominal cramping have been reported with CBD use. One case occurred in a woman ingesting about 25-75 mg of CBD oil three times weekly [85]. Another involved a boy taking approximately 700 mg/day for seizures, with symptoms appearing after starting a ketogenic diet [86].

THC Content and Drug Testing

CBD supplements can contain enough THC to cause a positive drug test for marijuana. One of 7 adults tested positive at just 0.39 mg THC/day [91]. Seven of 14 people tested positive after taking a full-spectrum CBD liquid providing approximately 0.8 mg THC daily for 4 weeks [93]. THC is fat-soluble and can be stored in body fat, potentially affecting drug tests for several days after stopping CBD use [1].

Product Safety Concerns

Over-the-counter CBD products may contain more or less CBD than stated on labels, and may contain contaminants [2]. A dangerous synthetic cannabinoid (AB-FUBINACA) has been found in some CBD products and has been linked to several deaths [94].

Special Populations

Children: The American Academy of Pediatrics has not endorsed cannabis/cannabinoid use in children due to concerns about brain development [1][2].

Pregnancy: Smoking cannabis during pregnancy has been linked to lower birth weight [2]. Delta-9-THC is on California's Proposition 65 list for reproductive harm [1].

Pets: In dogs, CBD (2 mg/kg twice daily) for one month caused an increase in alkaline phosphatase levels. Researchers recommend monitoring liver enzymes in dogs receiving CBD [95]. In cats, one of eight studied had a significant increase in ALT [96].

Drug Interactions

CBD is metabolized by the cytochrome P450 enzymes CYP3A4 and CYP2C19. By competing for these enzymes, CBD can reduce the metabolism of co-administered drugs, raising their blood levels. These interactions are dose-dependent — they have primarily been documented at high CBD doses, and lower doses may have more modest effects [1][82].

Anticonvulsants

Several hundred milligrams of CBD daily in epilepsy trials caused sizable increases in blood levels of clobazam, valproic acid, levetiracetam, felbamate, lamotrigine, and zonisamide [82][98]. Adding 50-300 mg of CBD per day to brivaracetam increased blood levels by 95-280% [99].

Warfarin (Blood Thinners)

CBD may increase the blood-thinning effects of warfarin. In one case, a man's INR began increasing several weeks after starting CBD for seizures, requiring a 30% reduction in warfarin dose [100]. A dose-dependent INR increase was also reported in another patient, requiring a 20% warfarin dose reduction [101].

Caffeine

Very high-dose CBD (1,500 mg) nearly doubled blood levels of caffeine via CYP1A2 inhibition [102].

THC

Very high-dose CBD (640 mg) increased the effects of delta-9-THC (20 mg), causing greater anxiety, sedation, memory difficulty, and cognitive impairment compared to THC without CBD [103].

Sedatives and Sleep Aids

CBD should be used with caution with sedative medications, as it may enhance their effects. One study found that 15 mg CBD with 5 mg melatonin did not increase side effects compared to either alone [35].

Levothyroxine

Levothyroxine may increase blood levels of CBD by inhibiting CYP3A4. Two children on high-dose CBD who were also taking levothyroxine showed a 4-fold increase in CBD exposure [104]. Co-administration may also increase levothyroxine effects [105].

Other Medications to Use with Caution

Because CBD can inhibit CYP3A4, CYP2C19, and (at high doses) CYP1A2, the following medications may be affected [82]:

• Macrolide antibiotics: clarithromycin, azithromycin
• Immunosuppressants: cyclosporine
• Statins: atorvastatin, simvastatin, rosuvastatin
• Cardiovascular: nifedipine, metoprolol, propranolol, flecainide, losartan, valsartan
• Psychiatric: haloperidol, risperidone, clozapine, fluoxetine, fluvoxamine, paroxetine, mirtazapine
• Other: sildenafil, testosterone, progesterone, omeprazole, ondansetron, clopidogrel, celecoxib, naproxen, carisoprodol, cyclophosphamide, efavirenz, enzalutamide
• Hepatotoxic drugs: acetaminophen, amoxicillin, nitrofurantoin, ketoconazole, verapamil — use with caution due to combined liver injury risk [82]

A study found that ketoconazole (400 mg) increased blood levels of CBD, while rifampicin (600 mg) decreased blood levels of CBD [106].

Dietary Sources

CBD is not an essential nutrient and is not found in the general food supply. It is derived exclusively from the Cannabis sativa plant.

Natural Sources

• Hemp plants: Cannabis sativa varieties bred to contain <0.3% THC by dry weight. CBD content varies by cultivar.
• Marijuana plants: Cannabis sativa varieties with >0.3% THC. Also contain CBD but in varying ratios to THC.

Hemp seeds and hemp seed oil, while nutritious (rich in omega-3 and omega-6 fatty acids, protein, and minerals), contain minimal to no CBD. The cannabinoids are concentrated in the flowers, leaves, and stalks of the hemp plant — not the seeds [1].

Common Product Forms

Product Type	Typical CBD Content	Notes
CBD oil/tincture	5-50 mg per mL	Usually in MCT oil or hemp seed oil base; taken sublingually or added to food
CBD capsules/softgels	10-50 mg per capsule	Easier to dose consistently
CBD gummies/edibles	5-30 mg per piece	Added sugars; dose accuracy varies
CBD topical cream/salve	100-1,000 mg per container	Applied locally; not for systemic absorption
CBD vape products	Varies	FDA has warned against vaping THC products; safety concerns
CBD beverages	10-60 mg per serving	Emerging category; limited efficacy data
Full-spectrum hemp extract	Varies	Contains CBD, trace THC, other cannabinoids, terpenes
CBD isolate	99%+ CBD	No other cannabinoids or terpenes

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