I’m sure we’re all well aware of the parody that has become CBD. As it’s now in just about everything – skincare, food, gummies, potato chips, and even water. Yes good old H20 is now being infused with CBD. Insert eye roll here.

While I’ve heard of the MANY benefits from others regarding CBD, I’m also wary knowing it’s a newer product without much research done on it. My interest was officially peaked when learning there’s a pharmaceutical grade CBD product with FDA approval (and is only available by prescription)

So I decided to cbDive head first into that research so that I could then make a well informed opinion on the matter.

This post is a combination of both my own research, as well as reader submissions from personal experience. While I value evidenced based research, it’s sometimes a little late to the game, especially in the supplement industry for new products. Which is why having a bit of citizen science sprinkled in with the hard science will hopefully paint a fuller picture of the mythical CBD land.

Before hopping into the research, let’s first talk about the different kinds of CBD and regulation.

DIFFERENT KINDS OF CBD

Hempseed oil vs CBD

Hemp Oil or “hempseed oil” is oil that’s been extracted from the seeds of the industrial hemp variety of the cannabis sativa plant. Hemp seeds are pressed and bottled (sometimes processed and refined) and then bottled. Hemp oil is rich in omega fatty acids, antioxidants, vitamin E, and protein. Hemp oil contains no CBD or THC. ( 20 )

CBD oil is also derived from the cannabis sativa (hemp) plant, but instead of using just the seeds, CBD is extracted from the flowers, leaves, stems, and stalks of matured hemp plants. CBD oil can legally contain up to 0.3% THC based on federal law, the psychoactive cannabinoid. Regulations vary state to state. ( 20 )

Different TYPES of CBD

1. Full spectrum: contains terpenes, flavonoids, and nutrients that don’t appear in hemp oil alone. The extracts contain all of the compounds that occur naturally in the plant where they were extracted. Reputable CBD oil will come with a certificate of analysis (COA) that details exactly what’s in the product. Look for one that is hemp derived vs marijuana derived, as marijuana derived CBD may contain varying amounts of THC. Hemp-derived, in contrast, is legally required to contain less than 0.3% THC. Because there may be some THC in the product (especially if it is marijuana-based, consuming this may lead to a positive result on a drug screen. ( 20 )
2. Broad-spectrum CBD: contain additional compounds found in the plant, including terpenes and other cannabinoids. In the case of broad-spectrum CBD, all of the THC is removed. Because there is no THC, it shouldn’t show up on a drug screen. ( 20 )
3. CBD isolate: pure CBD. It doesn’t contain additional compounds from the plant it was extracted from. CBD isolate typically comes from hemp plants. Hemp-based CBD isolates shouldn’t contain THC. If you want to avoid THC, ensure that you’re purchasing CBD isolate from a reliable source. Because there is no THC, it shouldn’t show up on a drug screen. ( 20 )

The legality of CBD

Is CBD Legal? Hemp-derived CBD products (with less than 0.3 percent THC) are legal on the federal level, but are still illegal under some state laws. Marijuana-derived CBD products are illegal on the federal level, but are legal under some state laws. Check your state’s laws and those of anywhere you travel. Keep in mind that nonprescription CBD products are not FDA-approved, and may be inaccurately labeled. ( 21 )

How does CBD work?

CBD works on our endocannabinoid system, cutely nicknamed the ECS. The ECS is involved in a variety of physiological processes including appetite, pain sensation, mood, and cognition, as well as basic life functions such as appetite, immune response, reproduction, and pain management ( 12 ). Because CBD functions as an indirect antagonist to human CB1 and CB2 receptors, some postulate that the presence of CBD prevents them from being overly activated, thereby protecting the nervous and immune systems from everyday stress. ( 18 )

Various CBD formulations have been tested in pre-clinical studies to have diverse medicinal properties, such as anti-nausea, anti-emetic, anti-tumor, anti-inflammatory, anti-depressant, anti-psychotic, and anti-anxiolytic; however, the variance in drug formulations used and limited sample sizes reduce the applicability of these studies in clinical applications ( 19  Only preclinical and pilot studies have been performed for any of these uses, and therefore there is little guidance for physicians if their patient is interested in trying CBD or hemp oils for these conditions. ( 1 )

So let’s dive into the research a bit.

I included many different types of studies, including: double-blind, placebo controlled, case reports, and systematic reviews. ALL HUMAN STUDIES. For the sake of organization, I’m using a systems based approach to separate the research. So let’s get going from head to toe.

Neurology

NEUROLOGY

The majority of the research on CBD in the neurology department is on seizures in both adult and pediatric populations.

SEIZURES

• The study: when combined with standard antiepileptic treatment, does CBD oil help decrease seizures in Dravet syndrome ( 2 )
  • Background: Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for
  • Type of study: double-blind, placebo-controlled trial
  • Length of study: 14 weeks
  • Who was studied: 120 children and young adults with the Dravet syndrome and drug-resistant seizures received either cannabidiol oral solution or placebo, in addition to standard antiepileptic treatment.
  • Dose: 20 mg per kilogram of body weight per day
    • Cannabidiol oral solution contained 100 mg of cannabidiol per milliliter.
    • All doses were administered twice daily. At the end of the treatment period, the cannabidiol and placebo solutions were tapered (10% each day) over a period of 10 day
  • Results: cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo BUT was associated with higher rates of adverse events (somnolence and elevated liver enzymes) ( 2 )
    • frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures.
    • average frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo
    • percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo
    • patient’s overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group
  • Adverse events: occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group.
    • Elevated levels of liver aminotransferase enzymes (alanine aminotransferase or aspartate aminotransferase level >3 times the upper limit of the normal range) led to withdrawal from the trial of 3 patients in the cannabidiol group and 1 in the placebo group. Overall, elevated aminotransferase levels occurred in 12 patients in the cannabidiol group and 1 in the placebo group. All these patients were also taking a form of valproate.

The study: does CBD help with intractable childhood onset epilepsy when added to baseline antiepleptic treatment ( 3 )

• • Who was studied: patients aged 1–30 years withintractable childhood-onset epilepsy with 4+ countable seizures with a motor component per 4 week period and on stable doses of antiepileptic drugs for at least 4 weeks before enrollment.
  • Length of study: 12 weeks
  • The dose: 99% pure oil-based cannabidiol extract of constant composition (Epidiolex, GW Pharmaceuticals, London, UK), in a 100 mg per mL sesame oil-based solution
    • CBD oil at a dose of 2–5 mg/kg per day divided in twice-daily dosing was added to the baseline antiepileptic drug regimen, then up-titrated by 2–5 mg/kg once a week until intolerance or a maximum dose of 25 mg/kg per day was reached
    • For the first 3 months of cannabidiol treatment, efforts were made to keep concomitant doses of antiepileptic drug constant. However, in some cases, sedation after addition of cannabidiol led to decreases in those antiepileptic drugs, as clinically indicated. No antiepileptic drug was withdrawn during the study.
  • Results: The median monthly frequency of motor seizures was 30·0 at baseline and 15·8 over the 12 week treatment period. The median reduction in monthly motor seizures was 36.5%.
  • Adverse reactions / reasons for withdrawal: allergy to the sesame oil vehicle, hepatoxicity, excessive somnolence and poor efficacy, gastrointestinal intolerance, worsening seizures, and hyperammonemia
    • more than 5% of patients were somnolence, decreased appetite, diarrhea, fatigue, convulsions, appetite changes, status epilepticus, lethargy, changes in concentrations of concomitant antiepileptic drugs, gait disturbance, and sedation. Most adverse events were mild or moderate and transient.
    • Five (3%) patients had mild to moderate thrombocytopenia; one (1%) patient had severe thrombocytopenia (8 × 109/L) that resolved when valproate was stopped. 11 (7%) patients had elevated liver function tests; most were mild but one patient had a significant increase in transaminases (recorded as hepatotoxicity) leading to discontinuation of cannabidiol. All patients with hepatic or platelet abnormalities were also taking valproate.
    • However, patients who were taking more than 15 mg/kg per day cannabidiol were more likely to report diarrhoea or related side-effects (eg, weight loss) than those taking doses less than 15 mg/kg per day

CAUTION with combining CBD with other pharmaceuticals, particularly neuro drugs

• Drug-drug interactions have not been evaluated in any detail either. However, it is known that CBD has an inhibiting effect on CYP isozymes, and so could potentially impact antiepileptic medication, as e.g. valproate and clobazam are metabolized via these isozymes. Further studies are needed to clarify these potential side effects before CBD trial. ( 12 )
• An 8-week-long clinical study, including 13 children who were treated for epilepsy with clobazam and CBD (oral; starting dose of 5 mg/kg body weight and raised to maximum of 25 mg/kg body weight), increased clobazam bioavailability (and over-sedation in patients), making it possible to reduce the dose of the antiepileptic drug, which in turn reduced its side effects. ( 13 )
• With increased CBD dose, significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen (anti-epileptic medications). Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with CBD. ( 14 )

Reader Submissions

• “Positive! Keeps my seizures to a bare minimum! Rarely have them now!”

PARKINSON’S:

• Patients were started at 5 mg/kg/day and increased by 2.5–5 mg/kg at 3–5 day intervals to a target dose of 20 mg/kg/day, which is the recommended dosage.This study reported decreases in the total score of the MDS-UPDRS, in the Depression Short Form, and in the Scales for Outcomes in Parkinson’s Disease (SCOPA)-Sleep-night Time Sleep score, as well as increases in the Change in Montreal Cognitive Assessment, and in the Anxiety Short Form,which all suggested positive outcomes. At each dosage tested, there were no serious side effects observed; however, there were reported increased diarrhea (85%), fatigue (61%) somnolence (69%), and elevated liver function tests (39%) ( 19 )

Psychiatry

PSYCHIATRY

GENERALIZED ANXIETY

The study: anxiolytic effects of cannabidiol (CBD) vs placebo in generalized social anxiety disorder: a preliminary report ( 4 )

• Who was studied: Ten right-handed men with generalized SAD, aged 20-33 years old with no comorbid psychiatric disorders
• Dose: 400mg CBD
• Results: acute administration of CBD, one of the main psychoactive constituents of Cannabis sativa, can reduce subjective anxiety in patients clinically diagnosed with an anxiety disorder, in this case SAD.
  • Relative to placebo, CBD was associated with significantly decreased subjective anxiety, reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus, and increased ECD uptake in the right posterior cingulate gyrus. These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.
  • single dose of CBD induced significant decreases in state anxiety before SPECT scanning in patients with SAD. These anxiolytic effects were detected before the anxiety-provoking situation (the tracer injection and scanning procedure), suggesting that CBD facilitates habituation of anticipatory anxiety in social phobia.
• Adverse outcomes: no side-effects were reported. This is consistent with previous studies in humans that have shown that CBD is a safe and tolerable compound, without major side effects when administered acutely by oral route, inhalation or intravenous injection

The study: Cannabidiol in anxiety and sleep: A large case series ( 17 )

• Type of study: the retrospective chart review
• Who was studied: 103 adult patients.
  • 72 adults presenting with primary concerns of anxiety or poor sleep.
• Dose: Nearly all patients were given CBD 25 mg/d in capsule form. If anxiety complaints predominated, the dosing was every morning, after breakfast. If sleep complaints predominated, the dosing was every evening, after dinner.
  • A handful of patients were given CBD 50 mg/d or 75 mg/d. One patient with a trauma history and schizoaffective disorder received a CBD dosage that was gradually increased to 175 mg/d.
  • The doses used in this study (25 mg/d to 175 mg/d) were much lower than those reported in some of the clinical literature. Researchers concluded that lower doses appear to elicit an adequate clinical response. Second, the current retail cost of CBD would make the use of 600 mg/d cost prohibitive.
• Results: In an outpatient psychiatric population, sleep scores displayed no sustained improvements during the 3-month study. Anxiety scores decreased fairly rapidly, and this decrease was sustained during the study period.
  • on average, anxiety and sleep improved for most patients, and these improvements were sustained over time. a more sustained response to anxiety than for sleep over time. Patient records displayed a larger decrease in anxiety scores than in sleep scores. The sleep scores demonstrated mild improvement. The anxiety scores decreased within the first month and then remained decreased during the study duration.
• Adverse effects: In this chart review, CBD was well tolerated in all but 3 patients.
  • Two patients discontinued treatment within the first week because of fatigue. Three patients noted mild sedation initially that appeared to abate in the first few weeks. One patient with a developmental disorder (aged 21 years) had to be taken off the CBD regimenbecause of increased sexually inappropriate behavior. The CBD was held, and the behavior disappeared. The behavior reappeared on redosing 2 weeks later, and the CBD regimen was formally discontinued. The treating psychiatrist thought this was related to disinhibition because the patient’s anxiety responded dramatically. One patient noted dry eyes
• Limitations:
  • naturalistic study, all patients were receiving open-label treatment, and there was no comparison group.
  • The large societal notoriety about cannabis and medical marijuana probably contributes to a larger-than-normal placebo effect.
    • Any study that explores efficacy in this therapy probably will struggle with a potentially inflated placebo effect that will make these determinations more difficult.
  • Most patients were also taking psychiatric medications and receiving other mental health services, such as counseling, which limits the ability to make any causal links to CBD treatment.

Other CBD uses for anxiety:

• CBD was shown to be helpful for decreasing anxiety through a simulated public speaking test at doses of 300 mg to 600 mg in single-dose studies ( 17 )
• CBD with nitrazepam found that high-dose CBD at 160 mg increased the duration of sleep. Another crossover study showed that plasma cortisol levels decreased more significantly when given oral CBD, 300 to 600 mg, but these patients experienced a sedative effect ( 17 )
• higher doses of CBD that studies suggest are therapeutic for anxiety, insomnia, and epilepsy may also increase mental sedation. Administration of CBD via different routes and long-term use of 10 mg/d to 400 mg/d did not create a toxic effect on patients. Doses up to 1500 mg/d have been well tolerated in the literature. ( 17 )

Reader Submissions

• “I used to take Xanax as needed for anxiety and then I discovered CBD flower. IT’s bought at dispensaries just like cannabis, it’s 100% CBD and 0% THC. It’s the only thing that help.”
• “I used to take it before bed and it would help me fall asleep but I’d wake up in a panic / heart racing?.”
• “I bought high quality cbd oil for my anxiety and I haven’t been able to tell a difference.”
• “Positive! Better sleep, emotional regulation, pain relief.”
• “It helped me sleep through the night when I used to wake up every few hours. I use charlottes web sleepy cbd gummies.”
• “Better sleep but sometimes too good.”
• “Great after a stressful shift when I can’t stop my mind from racing and need to sleep.”
• “Very positive and helpful for anxiety and sleep. Very calming.”
• “Didn’t make me fall asleep easier but it brought me a deeper, less interrupted sleep.”
• “So calming! Especially post-partum nerves.”
• “Used a CBD tincture to help with sleep a couple times and it worked, but so does melatonin. So it could have been a placebo effect! But I’ve had nothing negative happen from trying it.”
• “I’ve used it to help with food allergy reactions and stress! It’s been SO helpful for sleep.”
• I’ve used it to reset how I was responding to anxiety. Used for 1ish years and now I’m off.”
• “Love it, helps me sleep. Helps calm my mind.”
• “I put CBD in my coffee before quitting my job and it helped me not sob unprofessionally.”
• “With regular use, I’ve experienced reduced anxiety, emotiuonal stability, and better sleep.”
• “Charlotte’s web ‘sleep’ formula gummies…absolutely amazing!”
• “I started using CBD for pain but instead noticed after a week that I hadn’t had any anxiety.”
• “Positive experience. I use it for anxiety and insomnia!”
• “CBD good morning pills make me feel limitless. From medterra.”
• “Love high-CBN CBD for sleep”

POST-TRAUMATIC STRESS DISORDER

The study: Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Study ( 5 )

• a ten-year-old girl who was sexually abused and had minimal parental supervision as a young child under the age of five. Pharmaceutical medications provided partial relief, but results were not long-lasting, and there were major side effects. A trial of cannabidiol oil resulted in a maintained decrease in anxiety and a steady improvement in the quality and quantity of the patient’s sleep.
• chief issues included anxiety, insomnia, outbursts at school, suicidal ideation, and self-destructive behaviors.
• A trial of CBD supplements (25 mg) was initiated at bedtime, and 6-12 mg of CBD sublingual spray was administered during the day as needed for anxiety. A gradual increase in sleep quality and quantity and a decrease in her anxiety were noted. After 5 months, the patient was sleeping in her own room most nights and handling the new school year with no difficulties. No side effects were observed from taking the CBD oil.
• this supplement given 12 mg to 25 mg once daily appears to provide relief of key symptoms with minimal side effects. Our patient did not voice any complaints or discomfort from the use of CBD.

SUBSTANCE ABUSE

The study: Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report ( 6 )

• 27-year-old male who presented with a long-standing diagnosis of bipolar disorder and a daily addiction to marijuana. His presenting concerns included erratic behaviors, anxiety, inconsistent sleep patterns, and irritability.
• The initial regimen was 24 mg of the CBD oil, with 6 sprays as needed during the day and 2 sprays before sleep. The dosage was gradually decreased from 24 to 18 mg, with the patient using no sprays during the day and 6 sprays at bedtime.
• With a subsequent, gradual decrease in anxiety, the patient was able to maintain a regular sleeping schedule. The patient reported being less anxious and sleeping better since taking the CBD oil. He reported not using any marijuana since starting the CBD and was proud of his accomplishment of getting a job as a self-employed driver and continuing with teaching chess to children.

Other studies involving CBD and substance use disorder:

• One study administered CBD four times to patients that have abstained heroin use for at least 6 days prior to the first session, in one of two dosages, either 400 or 800 mg. Due to the small sample size (n=10), the two different dosage arms were combined to determine the efficacy in reducing cravings, which they reported a reduction of both in-clinic and out-clinic cravings; however, a larger sample size is needed to form more definitive conclusions. Additionally, no serious adverse effects were reported, and 4 of 6 participants reported non-serious adverse effects including diarrhea, drowsiness, increased appetite, change in urine color, and feeling down or irritable ( 19 )

SCHIZOPHRENIA

The study: Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia ( 9 )

• Study details: double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings.
• Who was studied: 42 acutely exacerbated schizophrenic patients who had met the DSM-IV criteria.
• Dose: participants received either cannabidiol or amisulpride starting with 200 mg per day each and increased stepwise by 200 mg per day to a daily dose of 200 mg four times daily (total 800 mg per day) each within the first week.
• Results: cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
  • Patients undergoing either cannabidiol or amisulpride treatment showed significant clinical improvement, assessed by the reduction in PANSS total score as well as for all subcategories of symptoms of schizophrenia
  • Compared with amisulpride, treatment with cannabidiol was associated with significantly fewer extrapyramidal symptoms, less weight gain, and lower prolactin increase—a predictor of galactorrhoea and sexual dysfunction
  • After 4 weeks of treatment, both drugs had reduced ratings on the Positive and Negative Syndrome Scale (PANSS) to a similar extent, but CBD was associated with fewer adverse effects.
• Side effects: cannabidiol displayed a markedly superior side-effect profile compared to anandamide

The study: Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial  ( 11 )

• Who was studied: 88 patients, aged 18–65 years of age with schizophrenia or a related psychotic disorder as defined by DSM-IV. They were required to have previously demonstrated at least a partial response to antipsychotic medication (i.e., they did not have treatment-resistant illness) and to have been receiving a stable dosage of antipsychotic medication for at least 4 weeks; this treatment was continued unchanged for the duration of the trial
• Dose details: Patients were randomly assigned in a 1:1 ratio to receive 1,000 mg/day of CBD (10 mL of a 100 mg/mL oral solution) or matching placebo (excipients alone), administered in two divided doses (morning and evening).
• Study duration: 6 weeks of treatment
• results: treatment alongside antipsychotic medication was associated with significant effects both on positive psychotic symptoms and on the treating clinicians’ impressions of improvement and illness severity. There were also improvements in cognitive performance and in the level of overall functioning, although these fell short of statistical significance.
• Adverse effects: only one-third of the patients in each group reported treatment-emergent adverse events. The majority of these were mild and resolved spontaneously, with no significant differences in frequency between the CBD and placebo groups

Other studies involving CBD and schizophrenia:

• Another 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600 mg/day) was performed in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. There was a significant decrease in the total score of the Positive and Negative Syndrome Scale (PANSS), which suggests a decrease in overall symptoms; however, there was no significant drug × time interaction, which means the effect of treatment did not depend on time. There were no serious adverse side effects observed in this study, and the only side effect observed in the CBD group compared to the placebo was sedation ( 19 )

PSYCHOSIS

The study: the effect of CBD oil on parkinson’s patients with psychotic symptoms

• One research group investigated the efficacy, tolerability and safety of CBD in psychotic patients with PD through an open-label4-week pilot study. They gave a first dose of 150 mg/day and then increased the dose by 150 mg/day each week for the remaining three weeks for a maximum dose of 600 mg/day during the fourth week. Serial neurological and physical assessments in the study found that CBD did not worsen motor symptoms or contribute any notable side effects, but it did significantly decrease psychosis symptoms ( 19 )
• a teenager with severe side effects of traditional antipsychotics was treated with up to 1500 mg/day of CBD for 4 weeks. No adverse effects were observed and her symptoms improved. The same positive outcome was registered in another study, where three patients were treated with a starting dose of CBD of 40 mg, which was ramped up to 1280 mg/day for 4 weeks( 13 ) 

BIPOLAR DISORDER

• In another study, patients met DSM IV criteria for bipolar I disorder experiencing a manic episode without comorbid conditions. Both patients received placebo for the initial 5 days and CBD from the 6th to 30th day (initial oral dose of 600 mg reaching 1200 mg/ day). From the 6th to the 20th day, the first patient (a 34-year-old woman) received adjunctive olanzapine (oral dose of 10—15 mg). On day 31, CBD treatment was discontinued and replaced by placebo for 5 days. The first patient showed symptoms improvement while on olanzapine plus CBD, but showed no additional improvement during CBD monotherapy. The second patient (a 36-year-old woman) had no symptoms improvement with any dose of CBD during the trial. Both patients tolerated CBD very well and no side-effects were reported. These preliminary data suggest that CBD may not be effective for the manic episode of BAD ( 16 )

Dermatology

DERMATOLOGY

• 3 cases of self-initiated topical cannabidiol use in patients with epidermolysis bullosa in an observational study. Epidermolysis bullosa is a rare blistering skin disorder that is challenging to manage because skin fragility and repeated wound healing cause itching, pain, limited mobility, and recurrent infections. One patient was weaned completely off oral opioid analgesics. All 3 reported faster wound healing, less blistering, and amelioration of pain with cannabidiol use. ( 7 )
• We must exercise caution in interpretation of these findings, because randomized, double- blind, controlled studies are necessary to provide credible evidence of the benefits of CBD in EB. This is an observational study, which has inherent bias. For example, responders are more likely to divulge use of CBD than nonresponders, potentially magnifying the perceived clinical benefits. There is also potential for bias because results are self-reported. Furthermore, the study lacked a vehicle control group for comparison. ( 7 )

Gastroenterology

GASTROENTEROLOGY

Ulcerative colitis

• in a randomized, double-blind, placebo-controlled, and parallel-group study design. Over 10 weeks, various dosages (50–250 mg) of Epidiolex were administered twice a day to 29 patients suffering from UC, and a placebo was given to 31 patients. ( 19 )
• Their primary goal was to observe changes in the Mayo score (an indicator of UC severity; < 2 = remission of UC), and their secondary outcomes included measuring irritable bowel syndrome responses, UC symptom measurements, and calprotectin levels. Decreases in the Mayo score (−2.0 in treatment compared to −1.2 in control) and in the levels of calprotectin in the patients’ fecal matter were observed in the treatment group. There were no serious adverseeffects reported by the treatment group and no mortality reported; however, 96.55% of the treatment group (76.44% of placebo group) reported some other adverse events, including dizziness (46%), somnolence (34%), and nausea (27%) ( 19 ).

Reader Submissions

• “I love Jannabis Wellness! I use her PCR hemp oil tincture to help manage IBS symptoms.”
• “I use CBD for Crohn’s disease pain! The only thing that’s ever eased my pain.”

PAIN / INFLAMMATION

PAIN / INFLAMMATION

• in the most recent review on the topic in 2018, researchers wrote that “an overwhelming body of convincing preclinical evidence indicates that cannabinoids produce antinociceptive effects in inflammatory and neuropathic rodent pain models.” Cannabidiol therefore represents an attractive option in chronic pain treatment, particularly in the context of opioid abuse, not only because of its potential efficacy but also because of its limited misuse and diversion potential as well as safety profile. More research will be needed because these were pilot human studies with small sample sizes, but they represent potential future areas of cannabinoid use in the clinical treatment of pain relief and opioid abuse ( 1 )

Reader Submissions

• “tremendously helps ease nerve pain.” – reader submission
• “my dad uses CBD cream for his arthritis and loves it” – reader submission
• “For me it has really helped with ankle tendinitis and chronic knee pain both from running”
• “I used it on my back to ease pain from Sciatica. It seems to relive it a little bit!”
• “Some brands help me with sleep a lot, and the CBD slaved also helped with my very inflamed knee after I fell directly onto it, it helped with pain and I like to think it helped to reduce a little of the inflammation.”

 

Safety profile / Adverse Effects:

• most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile ( 13 )
• CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects ( 13 )
  • For example, CBD can affect warfarin levels (a blood thinner)
    • In one case study, a patient was taking lamotrigine 400 mg and levetiracetam 1500 mg, both twice daily. He was also taking warfarin 7.5 mg daily with a goal International Normalized Ratio (INR) of 2–3. Prior to study entry, his INR had been stable for at least 6 months with levels ranging from 2.0 to 2.6
    • With CBD oil (5mg/kg), an increase in INR was noted. Warfarin dosage adjustments were made by primary care physician in effort to maintain an INR within his therapeutic range. At the most recent study visit his warfarin dose had been reduced by approximately 30%. The patient was followed clinically without bleeding complications.
  • CBD also affects the bioavailability of some seizure medications:
    • An 8-week-long clinical study, including 13 children who were treated for epilepsy with clobazam and CBD (oral; starting dose of 5 mg/kg body weight and raised to maximum of 25 mg/kg body weight), increased clobazam bioavailability (and over-sedation in patients), making it possible to reduce the dose of the antiepileptic drug, which in turn reduced its side effects. ( 13 )
    • With increased CBD dose, significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen (anti-epileptic medications). Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with CBD. ( 14 )
• Cannabidiol doses up to 300 mg/d have been used safely for up to 6 months, and doses of 1200 to 1500 mg/d were used in a study for up to 4 weeks. In the recent larger studies on CBD treatment for epileptic patients, CBD had associated adverse effects of somnolence, decreased appetite, and diarrhea noted in up to 36% of patients, although these adverse effects were less severe and less frequent when compared with the usual adverse effects of clobazam treatment. ( 1 )
• diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group. (children and young adults with Dravet syndrome) ( 2 )
  • Elevated levels of liver aminotransferase enzymes (alanine aminotransferase or aspartate aminotransferase level >3 times the upper limit of the normal range) led to withdrawal from the trial of 3 patients in the cannabidiol group and 1 in the placebo group. Overall, elevated aminotransferase levels occurred in 12 patients in the cannabidiol group and 1 in the placebo group. All these patients were also taking a form of valproate. (children and young adults with Dravet syndrome) ( 2 )
• Adverse reactions / reasons for withdrawal: allergy to the sesame oil vehicle, hepatoxicity, excessive somnolence and poor efficacy, gastrointestinal intolerance, worsening seizures, and hyperammonemia (pt ages 1-30 with intractable seizures)
  • more than 5% of patients were somnolence, decreased appetite, diarrhea, fatigue, convulsions, appetite changes, status epilepticus, lethargy, changes in concentrations of concomitant antiepileptic drugs, gait disturbance, and sedation. Most adverse events were mild or moderate and transient. (pt ages 1-30 with intractable seizures) ( 3 )
  • Five (3%) patients had mild to moderate thrombocytopenia; one (1%) patient had severe thrombocytopenia (8 × 109/L) that resolved when valproate was stopped. 11 (7%) patients had elevated liver function tests; most were mild but one patient had a significant increase in transaminases (recorded as hepatotoxicity) leading to discontinuation of cannabidiol. All patients with hepatic or platelet abnormalities were also taking valproate. (pt ages 1-30 with intractable seizures) ( 3 )
  • However, patients who were taking more than 15 mg/kg per day cannabidiol were more likely to report diarrhoea or related side-effects (eg, weight loss) than those taking doses less than 15 mg/kg per day (pt ages 1-30 with intractable seizures) ( 3 )
• Adverse effects: In a chart review, CBD was well tolerated in all but 3 patients.
  • Two patients discontinued treatment within the first week because of fatigue. Three patients noted mild sedation initially that appeared to abate in the first few weeks. One patient with a developmental disorder (aged 21 years) had to be taken off the CBD regimenbecause of increased sexually inappropriate behavior. The CBD was held, and the behavior disappeared. The behavior reappeared on redosing 2 weeks later, and the CBD regimen was formally discontinued. The treating psychiatrist thought this was related to disinhibition because the patient’s anxiety responded dramatically. One patient noted dry eyes (large case series of adults taking CBD for anxiety and sleep) ( 17 )
  • higher doses of CBD that studies suggest are therapeutic for anxiety, insomnia, and epilepsy may also increase mental sedation. Administration of CBD via different routes and long-term use of 10 mg/d to 400 mg/d did not create a toxic effect on patients. Doses up to 1500 mg/d have been well tolerated in the literature. ( 17 )

• non-serious adverse effects including diarrhea, drowsiness, increased appetite, change in urine color, and feeling down or irritable (using CBD to decrease substance use) ( 19 )
• most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile ( 13 )

Reader Submissions of No Effect

• “So neutral! I’ve tried different strengths, frequencies, routes of admin, and no effects.”
• “I’ve tried like 3 products – pens and two types of gummies and have never felt anything.”
• “Doesn’t work for me unless combined with THC. No matter how reputable the brand is.”
• “1 experience where it was great, 1 where it caused a migraine, and the rest neutral!”
• “I don’t feel like it does anything for me.”
• “I took CBD drops for every day for 30 days and felt no different (in terms of anxiety)

Be wary of labeling:

• Of tested online CBD products, 26% contained less CBD than labeled. Underlabeling is less concerning as CBD appears to neither have abuse liability nor serious adverse consequences at high doses; however, the THC content observed may be sufficient to produce intoxication or impairment, especially among children ( 8 )
• The discussion on the legal status of CBD revolves mainly around the question: is it a medicine or a natural food supplement? The main difference is that medicinal drugs are considered unsafe until proven safe, whereas food supplements are considered safe until proven other- wise. As a result, the central question becomes whether or not CBD is safe for consumers (children, elderly, patients) in large and unregulated quantities. Although there is only limited knowledge about the long-term effects of chronic use, or about drug-drug interactions between CBD and other medications, human studies have indicated that CBD is very well tolerated even up to a daily dose of 1,500 mg ( 18 )
• the risks to be assessed about CBD products may not have much to do with the pure compound CBD itself, but more with the unknown composition and quality of the products offered. In particular, we should be looking into the presence of contaminants in these concentrated extracts, and into incorrect or even misleading labels for the cannabinoid content of product ( 18 )
• The time has come for regulators to give CBD the attention it deserves in order to ensure that affordable, safe, and reliable CBD products are available to those who depend on them. ( 18 )
• unknown risks about long-term effects remain unaddressed, especially in vulnerable groups such as children, the elderly, and the chronically or terminally ill . ( 18 )

clinician’s guide to cannabidiol and hemp oils

• No rigorous safety studies have been done on “full-spectrum” phytocannabinoid oils because these products are relatively new, but the separate ingredients have been examined somewhat, generally with no major adverse effects noted. ( 1 )
• A considerable number of patients in these studies had elevated liver function test results, and the FDA recommends liver function tests before beginning Epidiolex treatment, as well as 1 month and 3 months after initiation of treatment; thus, physicians should be cautious in patients with known decreased hepatic function who choose to use CBD and hemp oils. ( 1 )

1.     Does it meet the following quality standards? a.     Current Good Manufacturing Practices (CGMP) certification from the US Food and Drug Administration b.     European Union (EU), Australian (AUS), or Canadian (CFIA) organic certification, National Science Foundation (NSF) International certification 2.     Does the company have an independent adverse event reporting program? 3.     Is the product certified organic or eco-farmed? 4.     Have their products been laboratory tested by batch to confirm tetrahydrocannabinol levels (THC) <0.3% and no pesticides or heavy metals?

 

CONCLUSION

• Most of the research done has been in animal models and has shown potential benefit, but clinical data from randomized controlled experiments remain limited.
• there is data (though limited) to speak to the efficacy for CBD for neurology conditions like seizures and Parkinson’s disease, psychiatric conditions such as insomnia, generalized anxiety, substance use/abuse, schizophrenia and other varieties of psychosis, as well as GI conditions like IBD, some skin conditions, and pain/inflammation.
• for the most part, the side effect profiles seem to be minor, including tiredness, diarrhea, and changes of appetite/weight.
• HOWEVER, more serious side effects such as elevated liver enzymes and changes in other drug bioavailability (seizure medications and warfarin reported on above) exist
• always speak to your healthcare provider prior to starting a new medication or supplement!

 

References

( 1 ) VanDolah, H.J., Bauer, B.A., Mauck, K.F. (2019). Clinicians’ guide to cannabidiol and hemp oils. Mayo Clinic Proceedings, 94(9), 1840-1851. Doi:  https://doi.org/10.1016/j.mayocp.2019.01.003

( 2 ) Devinsky, O., Cross, J.H., Laux, L., Marsh, E., Miller, I., NAbbout, R., … & Wright, S. (2017). Trial of cannabidiol for drug-resistant seizures in the dravet syndrome. The New England Journal of Medicine, 376(21), 2011-2020. DOI: 10.1056/NEJMoa1611618

( 3 ) Devinsky, O., Marsh, E., Friedman, D., Thiele, E., Laux, L., Sullivan, J., Miller, I., … & Cilio, M.R. (2015). Cannabidiol in patients with treatment-resistant epilepsy. The Lancet Neurology, 15(3), 270-278. DOI: 10.1016/S1474-4422(15)00379-8

( 4 ) Crippa, J.A.S., Derenusson, G.N., Ferrari, T.B., Wichert-Ana, L., Duran, F.L.S., Martin-Santos, R., Simoes, M.W. … & Hallak, E.C. (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. Journal of Psychopharmacology, 25(1), 121-130. DOI: 10.1177/0269881110379283

( 5 ) Shannon, S. & Opila-Lehman, J. (2016). Effectiveness of cannabidiol oil for pediatric anxiety and insomnia as part of posttraumatic stress disorder: A case report. The Permanente Journal, 20(4), 16-005.

( 6 ) Shannon, S. & Opila-Lehman, J. (2015). Cannabidiol oil for decreasing addictive use of marijuana: A Case Report. Integrative Medicine: A Clinician’s Journal, 14(6), 31-35.

( 7 ) Chelliah, M.P., Zinn, Z., Khuu, P., & Teng, J.M.C. (2018). Pediatric Dermatology, 35(4), e224-e227.  https://doi.org/10.1111/pde.13545

( 8 ) Bonn-Miller, M.O., Loflin, M.J.E., Thomas, B.F. et al. (2017). Labeling accuracy of cannabidiol extracts sold online. JAMA, 318(17), 1708-1709. Doi: 10.1001/jama.2017.11909

( 9 ) Leweke, F., Piomelli, D., Pahlisch, F. et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry 2, e94 (2012). https://doi.org/10.1038/tp.2012.15

( 10 ) Hindocha, C., Freemnan, T.P., Grabski, M. et al. (2018). Cannabidiol reverses attentional bias to cigarette c ues in a human experimental model of tobacco withdrawals. Addiction, 113(9), 1696-1705.  https://doi.org/10.1111/add.14243

( 11 ) McGuire, P., Robson, P., Cubala, W.J. et al (2018). American Journal of Psychiatry, 175(3), 225-231

( 12 ) Karl, T., Garner, B., & Cheng, D. (2017). The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease.Behavioural Pharmacology, 28(1), 142-160. https://doi.org/10.1097/FBP.0000000000000247

( 13 ) Iffland, K. & Grotenhermen, F. (2017). An update on safety and side effects of cannabidiol: A review of clinical data and relevan animal studies. Cannabis and Cannabinoid Research, 2(1), 139-154.

( 14 ) Gaston, T.E., Bebin, E.M, Butter, G.R., Liu, Y., & Szaflarski, J. P. (2017). Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia, 58(9), 1586-1592.  

https://doi.org/10.1111/epi.13852

( 15 ) Grayson, L., Vines, B. et al (2018). An interaction between warfarin and cannabidiol, a case report. Epilepsy Behavioral Case Reports, 9 ,10-11.

( 16 ) Zuardi, A.W., Crippa, J.A.S., Dursun, S.M et al. (2008). Cannabidiol was ineffective for manic episode of bipolar affective disorder. Journal of Psychopharmacology, 24(1), 135-137. https://doi-org.ezproxy.neu.edu/10.1177/0269881108096521

( 17 ) Shannon, S., Lewis, N., & Hughes, S. (2019). Cannabidiol in anxiety and sleep: A large case study. The Permanente Journal, 23, 18-041.

( 18 ) Hazekamp, A. (2018). The trouble with CBD Oil. Medical Cannabis and Cannabinoids, 1(1). 65-72. https://doi.org/10.1159/000489287

( 19 ) Pauli, C. S., Conroy, M., Vanden Heuvel, B. D., & Park, S. H. (2020). Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. Frontiers in Pharmacology, 11, 63. https://doi.org/10.3389/fphar.2020.00063

( 20 )  https://nuleafnaturals.com/hemp-oil-cbd-oil/

( 21 ) https://www.healthline.com/health/does-cbd-show-up-on-a-drug-test#takeaway

 

 

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