CBD Oil: Safety, Side Effects, and Drug Interactions

CBD Safety and Side Effects

CBD Oil: Safety, Side Effects, and Drug Interactions

The rising popularity of cannabidiol (CBD oil) as a treatment for dozens of conditions is in part due to its impressive safety profile. So how safe is CBD oil, and are there any side effects to look out for? Let’s take a look at what current research has to say.

How is cannabinoid research conducted?

Most of the cannabinoid and CBD research conducted to date has not been conducted on human beings. It has instead been conducted via animal studies (e.g. mice) or in vitro (meaning, in test tubes).

It’s pretty well known in the scientific and research communities that the results of animal studies don’t always translate to the human population. According to this 2006 research, human trials had the success rates of their animal-trial counterparts in only about one-third of cases.

Putting published research results into perspective

Before we cast judgement on the seeming lack of cannabinoid research conducted on actual humans, let’s get it into perspective and look at what goes on with pharmaceutical drugs. Also keep in mind that cannabis has been used therapeutically and safely for millennia.

Pharmaceutical-drug approvals based on one trial

According to a submission put forward to the British Medical Journal by CLEAR (Cannabis Law Reform UK), something like one third of pharmaceutical drugs are approved by the FDA for the US market based on just one clinical trial, many of which run for only a short period of time with low numbers of participants.

“What doctors don’t know about the drugs they prescribe”

The other issue of concern with regards to the approval of pharmaceutical drugs is the heavy bias of scientific journals towards publishing only positive findings. In a 2012 TEDMED talk called, “What doctors don’t know about the drugs they prescribe”, Dr Ben Goldacre talks about the “unflattering data that gets lost”.

Goldacre says that as a doctor himself, he prescribed drugs based on the positive research he had diligently read, not knowing that several other studies that had produced negative results for the same drugs had never seen the light of day. If he had known about the negative results, he may never have prescribed certain drugs that were proven in hindsight to be ineffective or even downright dangerous.

Goldacre points to Thalidomide as an infamous example of a drug that had no side effects on mice in animal trials, was promptly released to market as a safe anti-nausea drug for morning sickness in pregnant women, then wreaked havoc on a generation of babies. Whilst this was in the 1960s, he claims the problem of “negative results that go missing in action” is still extremely prevalent today.

Adverse and positive side effects of CBD oil

Our review of the available research confirms that the positive safety profile of CBD is well deserved. We’ve summarised the latest published research about positive and adverse effects of CBD oil. Keep in mind though, that CBD isolate may have been used instead of superior whole-plant extract in some of the trials and research. However, it is not always possible to know what kind of CBD has been used.

Published adverse side effects of CBD oil


Drug interactions (with Cytochrome P450 (CYP450) family of enzymes)

CYP450 enzymes in the liver help your body metabolise drugs. In some cases, CBD may make a drug more or less effective. If the drug is made more effective, you may need to take less of it and closely monitor that you do not take too much to avoid potential overdose.

unbiased, human studies on drug interactions and CBD.

Whilst considered an adverse effect, the upside of this is that CBD may help people to reduce the amount of toxic pharmaceutical drugs they are taking.

Various mouse studies have shown that CBD may do either, depending on which drug it is interacting with. Going forward, we need

P-glycoprotein activity

P-glycoprotein is a protein inside our cells that moves stuff around the body like nutrients, waste, toxins, and drugs. The therapeutic effect of many medications depends on how the P-glycoprotein interacts with it. Many of the drugs that are moved around by our P-glycoprotein are also metabolised by CYP450. Similarly, due to the effects of P-glycoprotein, in some cases CBD may make a drug more effective or less effective. If the drug is made more effective, you may need to take less of it and closely monitor that you do not take too much.

The research at LINK 4 concluded that CBD may weaken the placental barrier, allowing certain drugs that are not safe to a developing foetus to cross into the placenta. Note that this research does not conclude that CBD itself is harmful to a developing placenta.

CELL MIGRATION (no human studies)


Although one study cited no adverse effects on a developing embryo after CBD administration, other studies concluded that CBD was detrimental to a developing embryo.

Endocrine effects

While high concentrations of CBD in rats appeared to cause endocrine disruptions, low concentrations did not.


Drug interactions

Some human studies have found that CBD inhibits the metabolism of certain drugs, including warfarin and diclofenac (Voltaren). This means you would have to take less of them for them to be effective, and monitor dosage to make sure you do not take too much.

In other studies, one type of antibiotic reduced the bioavailability of CBD, whereas an antifungal did the opposite and significantly increased the concentrations of CBD in the body.

Physiological - Opioid addiction

Researchers noticed an increase in fatigue when CBD was coadministered with fentanyl in trials to treat opioid addiction.


General side effects

Patients with Dravet were given high doses of CBD in a three-month trial. In addition to reduced seizure frequency in 39% of participants, only mild side effects were noted, including fatigue, weight changes, and appetite changes.

Epidiolex trials (a GW Pharma CBD isolate) resulted in 50% of patients experiencing seizure reduction. Mild side effects reported included tiredness, diarrhoea, and inappetence. In some cases severe side effects were recorded including one case of liver damage, but researchers couldn’t confidently say if they were caused by the Epidiolex.

Whilst 45% of patients experienced reduced seizure frequency in another larger Epidiolex trial—where patients received the CBD isolate adjunctively with their existing anti-epileptic drugs—10% reported mild side effects including: exhaustion, tiredness, and diarrhoea.

Yet another GW Pharmaceuticals trial had a 79% side effect rate, including tiredness, reduced appetite, and diarrhoea. Again, reviews of this research have concluded that it is not possible to confidently say that these side effects were caused by the CBD.

Published positive effects of CBD oil


Tolerance to CBD

No human studies have shown that CBD users build up tolerance (which is a good thing).

Blood pressure, heart rate, body temperature, blood glucose, and others

No adverse effects noted in animal studies with short-term use of CBD.

Psychomotor functions

No adverse effects noted with long-term use.


Anxiety and depression

CBD was found to be anti-anxiolytic in several studies, and also reduced desire for sugar and decreased appetite and body weight.

Psychosis and Bipolar

Recognised as an antipsychotic, anti-oxidant, neuroprotective, mood stabiliser, CBD cancelled out anxiety and psychosis symptoms when given to people prior to a high dose of THC.

CBD reduced psychosis in patients with Parkinson’s, as well as having no side effects on their cognitive or motor functions.

High doses of CBD reduced severe side effects from anti-psychotic medications in a human case, as well as reducing psychotic behaviour in schizophrenia in human trials, without the side effects of powerful anti-psychotic pharmaceutical drugs.


CBD was shown to reduces heroin-seeking behaviour, with no effect on locomotor skills.

Human trials revealed “fast and progressive reduction in withdrawal, dissociative and anxiety symptoms” as well as no effect on hepatic (i.e. liver) enzymes.

CBD reduced the effect of the munchies in pot smokers and the amount of cigarettes smoked by tobacco addicts.


CBD is neuroprotective and promotes neurogenesis, as well as being beneficial to the cardiac, circulatory, and ventilatory systems. One study reported a reduction of short-term brain damage in stroke

Immune system

Immunomodulatory (adjusts the immune system) in cases of Multiple Sclerosis, arthritis, and Type 1 diabetes; anti-inflammatory and reduces neuroinflammation in Alzheimer’s. Anti-cancer properties in particular with regard to glioblastoma, breast, lung, prostate, and colon cancer.



Multiple studies have concluded that CBD has anti-cancer properties, including killing cancer cells while leaving healthy cells alone (apoptosis) and reducing the spread of cancer cells to secondary sites (metastasis).

Type 2 Diabetes

CBD was seen to reduce hyperglycaemia in Type 2 diabetes due to its anti-inflammatory and anti-oxidant nature.


CBD displayed anti-epileptic and anti-convulsant properties. Researchers could not find evidence to suggest any adverse effects such as genotoxicity,  mutagenicity, or neurotoxicity.



Opioid addiction

CBD coadministered with fentanyl did not increase the effects of the fentanyl.


When coadministered with antiepileptic drugs, CBD increased bioavailability of the drug, allowing its dosage to be reduced, and thus less side effects. This occurred in two human trials.


Opioid addiction

No respiratory or cardiovascular complications were noted when CBD was coadministered with fentanyl.

No negative effects on mood.

“Coadministration was safe and well tolerated, paving the way to use CBD as a potential treatment for opioid addiction.”



Human trials that administered CBD for around five months did not find any evidence of toxicity or severe side effects

General side effects

Patients with Dravet were given high doses of CBD in a three-month trial. In addition to reduced seizure frequency in 39% of participants, only mild side effects were noted, including fatigue.

Epidiolex trials (a GW Pharma CBD isolate) resulted in 50% of patients experiencing seizure reduction.


General side effects

In addition to improved quality of life, this trial saw no significant side effects in patients with Parkinson’s.


General side effects

Researchers found no difference in side effects between patients given CBD in the trial and those given a placebo.


Immune system

None of the patients given extremely high doses of CBD after bone-marrow or stem-cell transplants developed acute Graft Versus Host Disease (GVHD), i.e. where the donor cells attack the immune system. Sixteen months after the transplants, the incidence of GVHD was still relatively low. They also did not detect any severe side effects from the CBD.



Patients given CBD (and THCV, i.e. Δ(9)-tetrahydrocannabivarin) in this trial showed reduced resistin levels (a hormone that is implicated in obesity and insulin resistance) and increased incretin levels (a hormone that protects the pancreas).

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