cbd oil for opiods

No Benefit, Potential Harm, in Adding Cannabis to Opioids for Pain

MILWAUKEE — Adding cannabis to the mix offers no additional benefit to patients who are already taking prescription opioids for chronic pain — and may even increase negative outcomes, such as depression, new research suggests.

A survey of 450 opioid users with chronic pain showed no difference in pain intensity between the group who also reported using cannabis and the opioid use-only group.

In addition, the opioids plus cannabis group showed significantly higher scores on measures of depression and anxiety and had greater use of other substances, such as tobacco, alcohol, and cocaine.

“When people taking opioids for chronic pain become tolerant to the drugs and develop opioid-induced hyperplasia, they often will turn to cannabis for what they think is added pain treatment, but we found there were no reductions in pain,” lead author Andrew H. Rogers, PhD, from the University of Houston’s Department of Psychology in Texas, told Medscape Medical News.

The findings were presented here at the American Pain Society (APS) Annual Meeting 2019.

Unexpected Results

The study included 450 adults who reported prescription opioid use and took part in a questionnaire on mental health and substance use, conducted by the online survey platform Qualtrics.

Respondents (74% women; mean age, 38 years) reported chronic pain that included moderate to severe pain in the past 4 weeks.

Compared with those reporting opioid use only, those who reported opioid and cannabis co-use had significantly higher scores in depression on the Patient Health Questionnaire-Depression (PHQ-4, P = .001) and higher anxiety as assessed on the PHQ-4 Anxiety scale (P < .001).

Those reporting opioid and cannabis use also showed higher use of tobacco, alcohol, cocaine, and sedatives (all, P < .001).

There were no significant differences in measures of pain intensity (P = .20) or disability (P = .13) between the combination and opioid use-only groups on the Graded Chronic Pain Scale.

“We were hoping people using both opioids and cannabis would report lower pain, but we found there actually were no differences,” Rogers said.

“Furthermore, we also found people using both opioid and cannabis use had higher anxiety, depression, and substance use problems, which are clinically important problems that we as psychologists are interested in,” he added.

Different Brain Mechanism?

Rogers speculated that the assumption among many opioid users is that cannabis may affect the brain in a different way and provide some added benefits to opioids.

“I think there is a bidirectional effect, where the use of cannabis may be an avoidance strategy for anxiety and pain; but the repeated use of opioids and cannabis may only wind up worsening those symptoms,” he said.

In addition, “these individuals may be more difficult to treat for their pain and associated problems,” Rogers said.

The current findings are consistent with results from the larger Pain and Opioids in Treatment (POINT) study, which were published last July in The Lancet.

POINT was a 4-year prospective study of 1514 participants treated with prescription opioids for non­–cancer-related chronic pain. Results showed that among the 24% of patients who used cannabis for pain, the cannabis use was associated with greater pain severity and pain interference scores, lower pain self-efficacy scores, and greater generalized anxiety disorder scores.

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“We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation,” the POINT investigators, led by Gabrielle Campbell, PhD, University of New South Wales, Sydney, Australia, reported at the time.

Lack of Dosing Details

Commenting on the findings for Medscape Medical News, Mark Wallace, MD, professor of clinical anesthesiology and chief of the Division of Pain Medicine, University of California, San Diego, said that The Lancet study and the new study share a limitation that is common in the poorly-funded field of cannabis research: details on the doses of cannabis ingredients such as cannabidiol (CBD) and the psychoactive ingredient tetrahydrocannabinol (THC).

Although not involved with the current study, Wallace specializes in cannabis research at the UC San Diego Center for Medical Cannabis Research.

“The problem with these and other studies is we don’t know what kinds of doses they are getting,” he said.

“There’s basically not much difference between what’s sold on the street or sold at dispensaries. Patients who go out unsupervised often wind up with cannabis that had a very high dose of THC and they will say ‘I tried it and I hated it and it only made my pain worse,’ ” he added.

In the right balance, Wallace noted that cannabis can effectively treat pain and even often replace opioids; but he agrees that the two shouldn’t be mixed.

“I don’t advocate coadministration,” he said. “Most patients who come to me are chronic pain patients who are on opioids and want to get off. So as a general rule, I will taper them down from the opioids before introducing cannabis.”

Even then, treatments with cannabis are very tightly controlled and have specific recommendations regarding the ratios of CBT and THC and the frequency of administration, Wallace said.

Despite the recent onslaught of CBD-containing products in the marketplace, the only cannabis-based component to receive approval from the US Food and Drug Administration to date, as reported by Medscape Medical News, is the oral CBD solution Epidiolex (GW Pharmaceuticals).

This formulation uses high concentrations of CBD for the treatment of seizures associated with two rare and severe forms of epilepsy (Lennox-Gastaut syndrome and Dravet syndrome) in patients 2 years of age and older.

While the continued status of cannabis as a Schedule 1 substance under the Controlled Substances Act blocks federal funding for research, Wallace noted that California’s Proposition 64 is opening doors in that state and that taxes from recreational cannabis sales are being allocated to research and education.

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“The Center for Medical Cannabis Research here at UC San Diego just got its first installment from this, so hopefully this will allow for better progress in understanding all of these issues,” he said.

The study authors and Wallace have disclosed no relevant financial relationships.

Can cannabis help ease addiction?

Friends tease me because I’ve never smoked marijuana, yet study it. I started out looking at the impact of tetrahydrocannabinol (THC) — the cannabinoid present at the highest concentrations in the cannabis plant — on the developing brain. My question was: is there something going on such that your brain encountering THC before ever seeing an opioid changes your sensitivity to that opioid? I wanted to compare THC with another cannabinoid, so we looked at the second most prevalent cannabinoid in cannabis — cannabidiol (CBD). When we gave rats CBD, their heroin-seeking behaviour declined, opposite to THC.

Part of Nature Outlook: Opioids

What have your studies in people found?

We showed that CBD could decrease cravings prompted in heroin users when showing them videos of drug paraphernalia (Y. L. Hurd et al. Neurotherapeutics 12, 807–815; 2015). One week after their last dose of CBD, their cravings were still reduced, as was any prompt-induced anxiety. CBD has a protracted effect.

What does CBD do in the brain?

Many labs worldwide are racing to work out CBD’s full mechanism of action. It affects multiple systems: the CB1, CB2 and GPR55 cannabinoid receptors, vanilloid receptor 1 and the 5-HT1A receptor. It also enhances adenosine levels through the adenosine A1 receptor. But it’s not really potent at any one of these, and that’s something that I find fascinating. Neuropsychopharmacologists are trained that when something is high, they should get a hammer and knock it down. And when something is low, they need to get something big to drive it up. CBD operates in a milder way. Perhaps the reason that it doesn’t have considerable side effects is that it’s not dramatically knocking something down or pushing something up. It’s just fine-tuning different systems.

What are the challenges in CBD research?

The stigma and government regulations are big obstacles. In the United States, researchers had to get a licence for CBD: because it comes from the cannabis plant, it is classified as a schedule 1 controlled substance — even though, unlike THC, it doesn’t produce intoxication and isn’t addictive. Bureaucracy added at least six months to our studies. We had to get a specific type of safe for storing the CBD. A guard had to follow my clinical coordinator. I had to get an import licence, and an export licence.

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What has changed in the past year?

The US Agriculture Improvement Act of 2018 means that hemp (cannabis containing a low level of THC) is no longer classified, so if you’re studying hemp-derived CBD, you no longer need a licence. That has made a huge difference. The US National Institutes of Health has put out a request for grant applications on cannabinoid-related science. Now everybody is writing a CBD paper! But there’s a considerable shortage of medicinal-quality hemp-derived CBD. And CBD derived from cannabis is still a schedule 1 drug.

Does hemp-derived CBD differ from CBD derived from cannabis?

No, and this is the thing: chemistry is chemistry. If you’re only extracting and using CBD, and you can prove that you don’t have any THC in there, or less than 0.3%, it shouldn’t matter. Federally, CBD should not be classified at all. I think that its complete declassification would have a huge impact on being able to conduct the research that’s needed.

More from Nature Outlooks

What are you working at the moment?

In our rat model, we observed that CBD reverses some of the glutamate-related changes that heroin induces in the brain (J. Ren et al. J. Neurosci. 29, 14764–14769; 2009). So, we will study the neurotransmitter glutamate directly in the brain using neuroimaging in people with opioid-use disorder. We’ll complement that with studies in animals to get a handle on how CBD is working. Now that we have replicated the effects of CBD on drug craving and anxiety in pilot human studies, I want to see whether it works in the real world. We are seeking funding for a large study of CBD treatment in hundreds of people with heroin-use disorder, including those being treated with the heroin substitute methadone. Methadone doesn’t completely block cravings — it’s about harm reduction. Although methadone is an opioid, it is more manageable than heroin. We will be able to see, in a large population of people who are also on methadone, whether CBD can help to reduce the amount of opioids that they consume.

What drives your work on CBD?

Addiction is such a tough disorder. It’s not about morals. I don’t understand why we’re so nonchalant about the fact that in the past decade, almost half a million people in the United States have died from opioid drug overdoses. I think that if we can better understand addiction, we will be able to develop non-addictive treatments. When we have those medications, the stigma will be decreased. People will realize that someone can function normally. You won’t even know that they had a substance-use disorder.

Nature 573, S7 (2019)

This interview has been edited for length and clarity.

This article is part of Nature Outlook: Opioids, an editorially independent supplement produced with the financial support of third parties. About this content.