- Researchers conducted a study of cannabis extracts with 10 people living with HIV
- Cannabinoids did not harm the immune system or raise HIV levels
- Participants with pre-existing liver injury may have been more susceptible to liver inflammation
In the 1980s and early 1990s when there was no effective treatment for HIV, some people with this virus used cannabis to relieve certain symptoms, such as depression, nausea and loss of appetite/unintentional weight loss. Today, with effective HIV treatment widely available and used in Canada and other high-income countries, some people with HIV use cannabis to help relieve pain, anxiety and depression. It is also used for recreational purposes.
Although cannabis and its extracts are now legally available in Canada, they have not been extensively studied in people with HIV. A team of researchers at McGill University and the University of British Columbia conducted a pilot study of compounds found in cannabis—THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol)—given in pill form. The researchers recruited 10 people who took these pills for 12 consecutive weeks. The doses of cannabinoids were gradually increased over the course of the study. All participants were taking HIV treatment and had a suppressed level of HIV (less than 40 copies/mL).
Most participants did not experience any significant toxicity. There was no impact on assessments of the immune system, such as CD4+ and CD8+ cell counts and the CD4/CD8 ratio. There was also no impact on viral suppression.
However, two people had to prematurely leave the study—one for worsening anemia and the other because of persistently elevated levels of liver enzymes in the blood.
The researchers stated that larger studies are needed. They encourage scientists who are planning to conduct further studies of cannabinoids in people with HIV to screen participants for any liver conditions prior to dispensing cannabinoids and to monitor their liver enzyme levels in the blood while they are taking cannabinoids.
Study details
Researchers at McGill University recruited 10 participants between September 2021 and February 2022. The researchers had hoped to recruit a total of 26 people, but due to a number of factors, they could not achieve their target enrollment.
Participants were around 58 years of age and there were eight males and two females.
All participants underwent physical examination and regular blood tests.
Seven of the 10 people had last used cannabis between one and six months before entering the present study.
Cannabinoids
Researchers obtained capsules of cannabinoids from Tilray Brands in New York City for the study. Two versions of capsules were used in the study, as follows:
- a combination of THC + CBD in a 1:1 ratio (2.5 mg : 2.5 mg)
- only CBD – 200 mg
Participants were randomly assigned to receive either the combination of THC and CBD or CBD alone. Over the course of the study, the number of capsules taken was increased. If toxicity developed, participants could reduce their dose.
The researchers determined which doses to use based on results of clinical trials in people without HIV. In these other studies, cannabinoids were tested in people with chronic pain, multiple sclerosis, seizures and schizophrenia.
Results – Safety
According to the study team, at higher doses, “the majority of participants experienced [side effects] that were mild or moderate in severity.” Common side effects included the following:
- drowsiness during the daytime – 50%
- difficulty concentrating – 20%
- difficulty thinking clearly – 20%
- increased appetite – 20%
The researchers stated that these side effects resolved when the dose of cannabinoids was reduced.
Premature departure from the study
Two people prematurely left the study at the six-week mark because of the following safety concerns:
Case 1: A female in her early 30s entered the study with a moderate degree of anemia. Despite taking iron supplements during the study, the anemia did not resolve and subsequently became severe. To prevent further worsening of anemia, researchers had her withdraw from the study.
The researchers noted that at the six-week mark of the study analyses of her blood found higher-than-normal liver enzyme levels; however, they returned to normal within a week of her departure from the study (and cessation of the study drug). She had been taking capsules containing CBD only.
Case 2: A male in his early 60s unexpectedly developed very severe liver inflammation at week six. Researchers had him withdraw from the study, as they were concerned for his health. Despite leaving the study (and discontinuing the study drug; in his case, also CBD only), liver enzyme levels in his blood remained elevated. They referred the participant to liver specialists for evaluation. Scans of his liver found a mass on his pancreas gland. Biopsy of the mass revealed that it was cancer.
The researchers stated that other potential contributors to this participant’s increased risk of liver inflammation included the following:
- the presence of type 2 diabetes
- mild fatty liver (diagnosed by abdominal ultrasound)
- excess consumption of alcohol
- a possible interaction between his HIV treatment and cannabinoids
According to the researchers, it is unlikely that the cannabinoids played a role in the growth of his tumour.
Immunology and virology
As mentioned earlier, there was no significant impact of cannabinoids on the immune systems of participants. Specifically, there were no significant changes to CD4+ and CD8+ cells or to the CD4/CD8 ratio. Furthermore, all participants maintained a suppressed viral load throughout the study.
Abnormal blood sugar levels
Two people had type 2 diabetes diagnosed prior to entering the study. During the study, their blood sugar levels rose to very high levels. One person was taking THC + CBD and the other person was taking CBD only.
Quality of life and mood
Participants completed assessments of quality of life and mood during the study. Researchers found no significant change in these measures. The researchers stated that this lack of significant change may have occurred because “most participants had good quality of life and mood scores at [the start of the study].”
Bear in mind
Liver inflammation
The researchers noted that liver inflammation occurred in two participants when their dose of CBD was increased from 400 mg/day to 800 mg/day. According to the researchers, liver enzyme levels also temporarily rose with the use of CBD in some other studies (of people without HIV). They stated that liver enzyme levels in these studies “tend to normalize following dose reduction or…discontinuation [of CBD].” They also stated that these temporary increases in liver enzyme levels did not “seem to be of long-term clinical significance.”
The researchers reviewed their results and concluded that it was likely that people with pre-existing liver injury may be more susceptible to CBD-related liver inflammation. They referenced a previous study that found that further increases in liver enzymes were more likely in people who entered a CBD study with already elevated liver enzyme levels. In contrast, people who enrolled in the same study with normal liver enzyme levels were not likely to develop elevated levels while in the study.
Screening for liver injury in clinical trials
Based on the results of the present and other studies, the Canadian team had the following advice for scientists planning or conducting studies of CBD in people with HIV: Prior to initiating study medicines, participants with risk factors for fatty liver could undergo a specialized ultrasound scan of the liver (Fibroscan). Once in the study, participants’ liver enzyme levels could be closely monitored “to detect any subtle rises […] which may suggest undiagnosed [fatty liver].” If a Fibroscan machine is unavailable, the researchers suggested that simple blood tests (called Fibrosis-4 or Fib-4) could be done prior to initiation of cannabinoid-containing medicines.
Advising patients about safety
The researchers encouraged physicians to speak to their patients with HIV who may use cannabinoid-containing oils about their potential toxicity. Such oils are available without a prescription in Canada.
Diabetes
The researchers reviewed other studies of cannabinoids and found that they did not increase the risk of diabetes. They also mentioned that one study enrolled people with diabetes and there was no significant risk of raised or lowered blood sugar levels due to exposure to cannabinoids. Therefore, the researchers concluded that the cause(s) of rising blood sugar in two people with pre-existing diabetes while taking cannabinoids in their study could be a combination of the following factors:
- pre-existing health issues
- excess alcohol consumption
- an interaction among the many medicines that they were taking (the researchers did not provide further details on this)
Recruitment
The researchers had difficulty recruiting their target number of 26 participants. They stated that problems obtaining supplies of study medicines caused them to limit enrollment. There may have been other reasons that affected recruitment.
For the future
The present study is an important step in exploring the safety of cannabinoids in people with HIV. However, the researchers felt that “much additional work is needed to understand the safety and tolerability [of cannabinoids] in people with HIV.” In addition, further studies are needed to find the best dose(s) of CBD in this population.
Further analyses from this team about other effects of cannabinoids—such as their impact on excessive immune activation and inflammation, the burden of HIV-infected cells and the balance of bacteria and fungi in the gut—are expected in the future.
—Sean R. Hosein
Resource
REFERENCES:
- Mboumba Bouassa RS, Needham J, Nohynek D, et al. Safety and tolerability of oral cannabinoids in people living with HIV on long-term ART: A randomized, open-label, interventional pilot clinical trial (CTNPT 028). Biomedicines. 2022 Dec 7;10(12):3168.
- Furler MD, Einarson TR, Millson M, et al. Medicinal and recreational marijuana use by patients infected with HIV. AIDS Patient Care STDS. 2004 Apr;18(4):215-28.
- DeMarino C, Cowen M, Khatkar P, et al. Cannabinoids reduce extracellular vesicle release from HIV-1 infected myeloid cells and inhibit viral transcription. Cells. 2022 Feb 18;11(4):723.
- Costiniuk CT, Jenabian MA. Cannabinoids and inflammation: implications for people living with HIV. AIDS. 2019 Dec 1;33(15):2273-2288.