Cannabinoids may raise pain tolerance, not relieve pain itself

The belief that cannabinoids address chronic pain by relieving it has been challenged by a meta-analysis that finds cannabinoids have effects on pain thresholds that may, instead, make pain more tolerable.

The systematic review and meta-analysis comprised 18 placebo-controlled studies looking at the effect of plant-based or synthetic cannabinoids on experimental pain in 442 healthy participants. The conclusions were published Sept. 19 in JAMA Psychiatry.

“Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds,” wrote Martin J. De Vita and his colleagues, “but may not reduce the intensity of experimental pain already being experienced; instead, cannabinoids may make experimental pain feel less unpleasant and more tolerable, suggesting an influence on affective processes.”

Ten of the studies analyzed measured changes in pain thresholds and showed a small but significant association between cannabinoids and higher pain thresholds (95% confidence interval, 0.054-0.318; P = .006). Five studies examined pain unpleasantness, and showed that cannabinoids were associated with reduced unpleasantness ratings, compared with placebo (95% CI, 0.104-0.472; P = .002).

Among the eight studies that measured pain tolerance, a significant association was found between cannabinoid administration and higher pain tolerance (95% CI, 0.015-0.436; P = .04).

However, the 13 studies looking at pain intensity found no association between cannabinoid use and changes in the intensity of pain (CI, –0.120-0.154), nor were reductions in pain sensitivity to mechanical stimulation found in the three studies that measured mechanical hyperalgesia (95% CI, –0.059-0.244; P = .23).

The analysis did see significant effects according to the type of cannabinoid; plant-based cannabis had significantly stronger associations with reductions in pain unpleasantness compared to dronabinol and other synthetic THC preparations. However, both plant-based cannabis and dronabinol were associated with increases in pain tolerance, whereas other synthetic THC preparations were associated with significant reductions in pain tolerance.

The researchers also saw a dose-response effect: Higher doses were associated with a significant analgesic effect while lower doses were not.

Mr. De Vita, of the department of psychology at Syracuse (N.Y.) University, and his colleagues stressed that the systematic review and meta-analysis focused solely on studies of experimental pain, which “merely approximates features of clinical pain,” and specifically excluded individuals with chronic pain.

The absence of neuropathic pain data is “especially limiting, given that neuropathic pain is the primary condition for which modest empirical evidence exists that supports cannabinoid analgesia,” they wrote.

In particular, they drew attention to the finding that cannabinoids did not appear to have any effect on mechanical hyperalgesia, which they said suggests that cannabinoids might not address central sensitization in people with neuropathic pain.

The authors also raised the question of whether cannabinoids simply relieve pain by making people feel good or “high,” much like other intoxicating substances such as alcohol. They argued that the answer depends on what outcome is desired from treatment.

“If treatment aims to relieve pain without producing intoxication, psychoactive cannabinoids may not suffice,” they wrote. Ultimately, they said, the relief from pain experienced by some patients might be driven largely by an “affective rather than a sensory component.”

Among the limitations cited by the researchers is the focus on studies of experimental pain. “To produce evidence that supports the generalizability of the current findings, pain reactivity research must be conduced in clinical samples,” Mr. De Vita and his colleagues wrote.

The study was partly supported by the Syracuse University STEM Fellowship, and the National Institute on Alcohol Abuse and Alcoholism. No conflicts of interest were declared.

SOURCE: De Vita MJ et al. JAMA Psychiatry. 2018 Sep 19. doi: 10.1001/jamapsychiatry.2018.2503.

The belief that cannabinoids address chronic pain by relieving it has been challenged by a meta-analysis that finds cannabinoids have effects on pain thresholds that may, instead, make pain more tolerable.

The systematic review and meta-analysis comprised 18 placebo-controlled studies looking at the effect of plant-based or synthetic cannabinoids on experimental pain in 442 healthy participants. The conclusions were published Sept. 19 in JAMA Psychiatry.

“Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds,” wrote Martin J. De Vita and his colleagues, “but may not reduce the intensity of experimental pain already being experienced; instead, cannabinoids may make experimental pain feel less unpleasant and more tolerable, suggesting an influence on affective processes.”

Ten of the studies analyzed measured changes in pain thresholds and showed a small but significant association between cannabinoids and higher pain thresholds (95% confidence interval, 0.054-0.318; P = .006). Five studies examined pain unpleasantness, and showed that cannabinoids were associated with reduced unpleasantness ratings, compared with placebo (95% CI, 0.104-0.472; P = .002).

Among the eight studies that measured pain tolerance, a significant association was found between cannabinoid administration and higher pain tolerance (95% CI, 0.015-0.436; P = .04).

However, the 13 studies looking at pain intensity found no association between cannabinoid use and changes in the intensity of pain (CI, –0.120-0.154), nor were reductions in pain sensitivity to mechanical stimulation found in the three studies that measured mechanical hyperalgesia (95% CI, –0.059-0.244; P = .23).

The analysis did see significant effects according to the type of cannabinoid; plant-based cannabis had significantly stronger associations with reductions in pain unpleasantness compared to dronabinol and other synthetic THC preparations. However, both plant-based cannabis and dronabinol were associated with increases in pain tolerance, whereas other synthetic THC preparations were associated with significant reductions in pain tolerance.

The researchers also saw a dose-response effect: Higher doses were associated with a significant analgesic effect while lower doses were not.

Mr. De Vita, of the department of psychology at Syracuse (N.Y.) University, and his colleagues stressed that the systematic review and meta-analysis focused solely on studies of experimental pain, which “merely approximates features of clinical pain,” and specifically excluded individuals with chronic pain.

The absence of neuropathic pain data is “especially limiting, given that neuropathic pain is the primary condition for which modest empirical evidence exists that supports cannabinoid analgesia,” they wrote.

In particular, they drew attention to the finding that cannabinoids did not appear to have any effect on mechanical hyperalgesia, which they said suggests that cannabinoids might not address central sensitization in people with neuropathic pain.

The authors also raised the question of whether cannabinoids simply relieve pain by making people feel good or “high,” much like other intoxicating substances such as alcohol. They argued that the answer depends on what outcome is desired from treatment.

“If treatment aims to relieve pain without producing intoxication, psychoactive cannabinoids may not suffice,” they wrote. Ultimately, they said, the relief from pain experienced by some patients might be driven largely by an “affective rather than a sensory component.”

Among the limitations cited by the researchers is the focus on studies of experimental pain. “To produce evidence that supports the generalizability of the current findings, pain reactivity research must be conduced in clinical samples,” Mr. De Vita and his colleagues wrote.

The study was partly supported by the Syracuse University STEM Fellowship, and the National Institute on Alcohol Abuse and Alcoholism. No conflicts of interest were declared.

SOURCE: De Vita MJ et al. JAMA Psychiatry. 2018 Sep 19. doi: 10.1001/jamapsychiatry.2018.2503.

The belief that cannabinoids address chronic pain by relieving it has been challenged by a meta-analysis that finds cannabinoids have effects on pain thresholds that may, instead, make pain more tolerable.

The systematic review and meta-analysis comprised 18 placebo-controlled studies looking at the effect of plant-based or synthetic cannabinoids on experimental pain in 442 healthy participants. The conclusions were published Sept. 19 in JAMA Psychiatry.

“Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds,” wrote Martin J. De Vita and his colleagues, “but may not reduce the intensity of experimental pain already being experienced; instead, cannabinoids may make experimental pain feel less unpleasant and more tolerable, suggesting an influence on affective processes.”

Ten of the studies analyzed measured changes in pain thresholds and showed a small but significant association between cannabinoids and higher pain thresholds (95% confidence interval, 0.054-0.318; P = .006). Five studies examined pain unpleasantness, and showed that cannabinoids were associated with reduced unpleasantness ratings, compared with placebo (95% CI, 0.104-0.472; P = .002).

Among the eight studies that measured pain tolerance, a significant association was found between cannabinoid administration and higher pain tolerance (95% CI, 0.015-0.436; P = .04).

However, the 13 studies looking at pain intensity found no association between cannabinoid use and changes in the intensity of pain (CI, –0.120-0.154), nor were reductions in pain sensitivity to mechanical stimulation found in the three studies that measured mechanical hyperalgesia (95% CI, –0.059-0.244; P = .23).

The analysis did see significant effects according to the type of cannabinoid; plant-based cannabis had significantly stronger associations with reductions in pain unpleasantness compared to dronabinol and other synthetic THC preparations. However, both plant-based cannabis and dronabinol were associated with increases in pain tolerance, whereas other synthetic THC preparations were associated with significant reductions in pain tolerance.

The researchers also saw a dose-response effect: Higher doses were associated with a significant analgesic effect while lower doses were not.

Mr. De Vita, of the department of psychology at Syracuse (N.Y.) University, and his colleagues stressed that the systematic review and meta-analysis focused solely on studies of experimental pain, which “merely approximates features of clinical pain,” and specifically excluded individuals with chronic pain.

The absence of neuropathic pain data is “especially limiting, given that neuropathic pain is the primary condition for which modest empirical evidence exists that supports cannabinoid analgesia,” they wrote.

In particular, they drew attention to the finding that cannabinoids did not appear to have any effect on mechanical hyperalgesia, which they said suggests that cannabinoids might not address central sensitization in people with neuropathic pain.

The authors also raised the question of whether cannabinoids simply relieve pain by making people feel good or “high,” much like other intoxicating substances such as alcohol. They argued that the answer depends on what outcome is desired from treatment.

“If treatment aims to relieve pain without producing intoxication, psychoactive cannabinoids may not suffice,” they wrote. Ultimately, they said, the relief from pain experienced by some patients might be driven largely by an “affective rather than a sensory component.”

Among the limitations cited by the researchers is the focus on studies of experimental pain. “To produce evidence that supports the generalizability of the current findings, pain reactivity research must be conduced in clinical samples,” Mr. De Vita and his colleagues wrote.

The study was partly supported by the Syracuse University STEM Fellowship, and the National Institute on Alcohol Abuse and Alcoholism. No conflicts of interest were declared.

SOURCE: De Vita MJ et al. JAMA Psychiatry. 2018 Sep 19. doi: 10.1001/jamapsychiatry.2018.2503.