Cannabis for HIV-Related Conditions
Clinicians should open the door to a discussion.
Cannabis use is high among people with HIV: A recent nationally representative sample indicates that 8% of Americans with HIV use cannabis daily and more than one-quarter use it on a nondaily basis.1 Although a survey of cannabis users with HIV in Montreal found that the most common reason for cannabis use was pleasure, majorities of users also reported consuming the plant for various medicinal purposes, including reduction of pain, anxiety, and stress.2
How Effective Is Cannabis for Managing Conditions Associated With HIV?
“Just like almost all cannabis research, [the research on cannabis in HIV] is relatively minimal,” says Robert Cook, MD, MPH, a professor of epidemiology at the University of Florida Health who researches the health effects of cannabis in people with HIV. There’s significant evidence that cannabis is useful for treating HIV-associated pain, but there’s less clarity about how it affects other symptoms.
The State of the Research
A key problem is that the body of research on cannabis and HIV is not only small but also plagued by weak study design. Deepika Slawek, MD, MS, MPH, an assistant professor of internal medicine at the Albert Einstein College of Medicine who studies how cannabis affects inflammation and chronic pain in HIV, says, “The strength and the quality of the evidence is not great.” This is largely due to the regulatory environment surrounding cannabis research, which makes it hard to do randomized controlled trials. “A lot of the research that we have on the use of cannabis for symptoms among people with HIV are observational studies,” she says. “It’s great that they’re done, and it’s what we have access to at this point, but they’re not the same quality as the studies that we would see for other pharmaceutical medications.”
That said, several good-quality (albeit small and of short duration) randomized, placebo-controlled clinical trials of cannabis have been conducted among people with HIV. “It appears that many patients [with HIV] have been open to trying cannabis to treat some of these conditions and see if there’s a benefit. So people with HIV have been at the forefront of cannabis research over the past 20 years,” says David Grelotti, MD, an associate clinical professor of psychiatry and medical director of the Center for Medicinal Cannabis Research at the University of California, San Diego, and a specialist in HIV psychiatry.
So far, the cannabis product that has received the most study in published clinical trials among people with HIV is smoked whole-plant cannabis, which has been used in most research on neuropathic pain, anorexia and weight loss, and sleep, according to Grelotti. Some studies have also included dronabinol (synthetic THC). By contrast, federal regulations have meant there’s little to no research on many of the newer products popular with consumers, such as topicals, edibles, nabiximols, and isolated CBD.
More than one-half of people with HIV experience chronic pain,3 and it’s here that cannabis may have the greatest potential for benefit. “By far the strongest evidence [for a therapeutic benefit of cannabis is] for pain,” Slawek says—a point that she says is true in the context of HIV as well as in a broader context.
In total, there are approximately 30 randomized clinical trials that have examined the efficacy of cannabis for chronic pain.4 Though most of these studies examined pain stemming from causes other than HIV, they have generally shown that cannabis products are effective for pain regardless of the cause. Thus, the 2017 report of the National Academies of Sciences, Engineering, and Medicine concluded that “there is substantial evidence that cannabis is an effective treatment for chronic pain in adults.”4
As for clinical trials focusing specifically on cannabis for pain in people with HIV, there are two. A 2007 randomized placebo-controlled trial of 50 participants found that those who smoked cannabis saw a reduction in daily pain of 34% (the median percentage), whereas those on placebo saw a reduction of only 17%. Fifty-two percent of those in the cannabis group saw a reduction in pain of more than 30% as compared with only 24% in the placebo group.5
Similarly, a 2009 randomized crossover trial of 28 individuals with HIV-related neuropathic pain likewise found that smoked cannabis produced substantial reductions in pain intensity as compared with placebo. Forty-six percent of participants in this trial achieved pain reduction of 30% or more using cannabis, compared with only 18% who achieved that level of pain reduction on placebo.6
Nausea and Vomiting
Nausea and vomiting are common symptoms of HIV, and both are also common side effects of the antiretroviral therapies used to treat the virus.7 Several dozen clinical trials have examined the effectiveness of cannabinoids (specifically, dronabinol and nabiximols) for nausea and vomiting, but the vast majority of these studies have involved patients receiving chemotherapy for cancer, rather than individuals with HIV. The studies consistently show a benefit of cannabinoids for nausea, leading the authors of the 2017 National Academies report to say there is “conclusive” evidence to support use for this purpose in individuals taking chemotherapy4; however, the evidence is generally low in quality and the effects haven’t reached statistical significance in all studies.8,9
Only one trial has examined the effects of cannabinoids on nausea specifically in the context of HIV. It was a 2005 trial of 139 patients with AIDS-related anorexia, and it found that a 2.5-mg twice-daily dose of dronabinol was linked to a decrease in nausea for 20% of participants (compared with 7% of participants on placebo).10 Unfortunately, this difference wasn’t significant, and the quality of this evidence has been judged to be very low.11
Individuals with HIV tend to have more sleep problems—including difficulty falling asleep, shorter sleep duration, and greater daytime drowsiness—than do those without HIV. It’s estimated that more than 30% of individuals with HIV have sleep disorders, as opposed to a prevalence of only 10% in the general population.12
Two clinical trials involving people with HIV suggest that smoked cannabis has benefits for sleep, making it easier to fall asleep and improving sleep quality.13,14 However, these benefits appear to be evident only in the short term. A randomized placebo-controlled clinical trial of dronabinol in people with HIV found that although participants on dronabinol saw temporary improvements in sleep quality, these benefits only lasted for the first eight days of dosing.15 This is consistent with evidence outside the HIV context indicating that cannabis has short-term benefits for sleep but that users develop tolerance to the effects and the benefits are temporary.16
There’s some evidence that, among the general population, cannabis use actually has negative effects on sleep health over the long term.16 Intriguingly, however, several studies suggest that these same negative effects don’t occur in the HIV-spositive population.12,17 Thus, even though cannabis may not have a long-term benefit for sleep, individuals with HIV may not be subject to the same sleep-related harms of cannabis as other populations.
Inflammation and Immunomodulation
Antiretroviral drugs suppress HIV but don’t eliminate it, so the virus remains dormant in the body even with effective treatment. “It’s dormant, [but] it’s still there,” Grelotti says. “And it’s thought that the fact that it’s there does send a signal to your immune system that there is a bit of an infection there,” which has an inflammatory effect. That inflammation, in turn, drives comorbidities such as heart disease and diabetes.
Cross-sectional studies of people with HIV have found inconsistent associations of cannabis and immune function.18 However, a longitudinal study of people with HIV and hepatitis C coinfection suggested that cannabis use doesn’t have deleterious effects. Specifically, it found no link between cannabis use and levels of CD4+ and CD8+ T cells, which are critical for proper immune function.19
Several recent observational studies suggest that cannabis use may in fact reduce systemic inflammation and temper harmful immune activation in individuals with HIV. Specifically, one analysis of 198 people living with HIV grouped participants into heavy, medium, or occasional cannabis users. It found that all groups had comparable levels of CD4+ and CD8+ T cells overall, but that heavy users had lower frequencies of activated CD4+ and CD8+ T cells compared with people who didn’t consume cannabis. Heavy users also had lower frequencies of proinflammatory monocytes as well as lower levels of antigen-producing cells that secrete proinflammatory cytokines and tumor necrosis factor-alpha– producing cells.20 Similarly, another study found that cannabis users had lower levels of proinflammatory CD16+ monocytes as well as lower levels of the proinflammatory factor inducible protein 10.21 Most recently, in 2020, another group of researchers found that recent cannabis use was linked to lower levels of various inflammatory markers, both in cerebrospinal fluid and in the blood.22
There’s strong evidence that HIV infection is linked to neurocognitive impairments, even in the age of effective antiretroviral treatments. Among other things, HIV infection is associated with impaired motor skills, difficulties with executive function, slower information processing, and poorer episodic memory.23-25 Meanwhile, cannabis is independently associated with impairments in cognitive function and memory.26 There’s concern, therefore, that cannabis use could compound the cognitive strain already felt in HIV, exacerbating problems with cognition and memory.24
A 2004 study provides some evidence to support this theory of compounding negative effects of cannabis and HIV on cognition and memory: The authors reported a synergistic negative effect of HIV and cannabis use in people with advanced HIV, especially with respect to memory.27 However, the evidence for a negative effect of cannabis is mixed; a 2017 study of 215 adults with HIV found that current cannabis use was significantly associated with poor performance on one measure of cognition but not on two other measures. And lifetime cannabis use wasn’t associated with performance on
any of the three cognitive measures.28 In a sample of 1,920 men from the Multicenter AIDS Cohort Study, cannabis use was linked with worse cognitive processing speed, but the magnitude of effect wasn’t clinically meaningful.29
In several studies, chronic cannabis use has been linked to reduced gray matter volumes in both HIV-positive and HIV-negative individuals, but at least one study suggests that the risk of adverse cognitive outcomes isn’t any larger in people with HIV than in those not infected.30
Intriguingly, a few recent studies have suggested that cannabis use might in fact have some cognitive benefits in people with HIV.31 Specifically, in a racially and ethnically diverse sample of 679 adults with HIV, cannabis exposure was linked to a lower risk of neurocognitive impairment and to higher verbal fluency and learning performance.32 In another sample of 857 adults between 50 and 64 years of age, some with HIV and some without, history of cannabis use disorder was linked to neurocognitive “superaging” (that is, neurocognitive resilience).33 An additional study of 75 participants, some with HIV and some without, found that cannabis use was associated with better blood-brain barrier function in people with HIV, with blood-brain barrier function being an important marker of cognitive function.34
Cook believes further research could affirm a neuroprotective benefit of cannabis in HIV. “I do think it has potential,” he says. “I do believe components of it could be anti-inflammatory, [and] I do think people with HIV are dealing with chronic inflammation that probably corresponds to some type of brain inflammation,” which would lead to cognitive dysfunction.
For now, however, the reality is that “the evidence [about the neurocognitive effects of cannabis in HIV] is so mixed,” Slawek says. “Again, the great conundrum in the research on cannabis—the quality of all of these studies is not great. All of them are observational studies. All of them define cannabis use differently, [and] they all use different measures of cognition.”
There has been concern that people with HIV who use cannabis may have worse viral suppression than do nonusers, on the grounds that users may be less likely to take prescribed antiretroviral therapy. The evidence on this point is conflicting, with some research suggesting that cannabis use reduces adherence to therapy, while other research suggests no effect.35
Independent of the question of adherence to therapy, there’s some evidence that cannabis use contributes to viral suppression in people with HIV. Data from a pair of longitudinal observational cohorts of injection drug users who had recently become infected with HIV showed that cannabis use was strongly linked to lower viral load.36 Furthermore, a longitudinal study of 48 HIV-positive men found that cannabis use was linked to faster decay of HIV DNA. These findings are consistent with evidence from a study of simian immunodeficiency virus in macaques, which showed that administration of cannabis was linked to lower viral load and attenuation of disease progression.37 It’s also consistent with in vitro evidence showing that cannabinoids reduce HIV replication and cellular infection rates.38,39
“Cannabis alone cannot manage HIV disease,” Grelotti says. However, the evidence for the impact of cannabis on viral suppression “just reinforces this idea that maybe cannabis is having an immunomodulatory effect […] that may be helpful for HIV.”
Recommendations for Clinicians
Many clinicians are wary of cannabis, both in the context of HIV and beyond. But according to Slawek, physicians need to recognize that patients are using cannabis regardless of their physicians’ feelings. “As an HIV clinician and as someone who talks to my patients a lot about medical cannabis, I think the bottom line is that the horse is out of the stall,” she says. “Whether we as clinicians are supportive of that or not, a lot of our patients are going to use it and be asking about it. So, the most important thing for us to do is have a decent idea of what the evidence shows us, even if that evidence is murky.”
Although cannabis is no panacea and should be used carefully, Grelotti encourages physicians to consider it as an option for certain patients after carefully weighing the risks and the benefits. “There is a potential harm [with cannabis as] for any drug,” he says, noting that some people can experience intolerable side effects. Thus, Grelotti doesn’t necessarily recommend cannabis as a first-line treatment for HIV-associated conditions. For patients experiencing pain, for example, he says, “One of the things you might recommend first is physical therapy or some non–drug-related treatment.”
On the other hand, cannabis doesn’t have the same negative impacts as alcohol or other illicit drugs such as cocaine, heroin, or methamphetamine, and for most people the side effects will be comparable to any other medication they might take. “It is always important to consider the individual,” Grelotti says. “For a patient who doesn’t have significant side effects, it could be quite helpful and even life-changing.”
If patients do opt to try cannabis, Cook cautions clinicians to pay attention to possible drug-drug interactions and to be alert that patients could develop dependency. For any patients with advanced HIV/AIDS who are heavily immunosuppressed, physicians should also be attuned to the possibility that cannabis can be contaminated with mold and should encourage patients to be extra cautious about the source of the cannabis products they consume.
Cook’s most important piece of advice, however, is simply to establish open communication with patients. “There’s a stigma about medical marijuana,” he says, so patients don’t feel comfortable sharing what they’re using. “Open the door so that patients can talk about it.”
— Jamie Santa Cruz is a health and medical writer in the greater Denver area.
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