A new randomized clinical trial has found that a single high dose of a sublingual cannabis formulation containing equal amounts of THC and CBD reduced morphine use by nearly 48 percent among hospital patients suffering from severe acute radicular pain. The study, published October 9, 2026 in the Journal of Cannabis Research, compared two cannabinoid doses with placebo while allowing patients to control their own intravenous morphine use during the following 24 hours.
Patients receiving the higher cannabinoid dose consumed an average of 17.4 milligrams of morphine compared with 33.2 milligrams in the placebo group, a difference of approximately 47.6 percent. Just as importantly, pain scores were not significantly worse among the patients using less morphine. Researchers say the result provides new evidence that certain cannabinoid formulations may have an opioid-sparing effect, potentially allowing patients to achieve comparable pain control while using substantially less opioid medication. The trial was small and involved only 69 participants, however, making larger studies necessary before the strategy could become a standard part of acute pain treatment.
Researchers Tested Cannabis Alongside Morphine in Severe Radicular Pain
The trial was conducted at Hadassah Hebrew University Medical Center in Jerusalem and enrolled adults who arrived at the emergency department with acute radicular pain severe enough to rate at least six on a 10-point visual analog pain scale. Radicular pain occurs when a spinal nerve root becomes irritated or compressed, commonly because of a herniated disc or another structural spinal problem. Pain can radiate from the lower back through the buttock and leg, producing the characteristic symptoms commonly described as sciatica. Participants had their diagnosis confirmed using CT or MRI imaging before entering the study.
Researchers screened 246 potentially eligible patients, of whom 69 ultimately consented and were randomized. Twenty-six received the higher cannabinoid dose, 21 received a lower dose and 22 received placebo. All patients had access to intravenous morphine through patient-controlled analgesia, a system that allows a hospitalized patient to administer a predetermined dose by pressing a button when additional pain relief is required. Because the machine records each dose, investigators could objectively measure exactly how much morphine participants used rather than relying on memory or self-reported medication consumption.
The High Dose Contained 19.8 Milligrams Each of THC and CBD
The experimental treatment was delivered under the tongue as a cannabis-derived formulation containing THC, CBD and terpenes. Patients assigned to the high-dose group received 19.8 milligrams of delta-9 THC and 19.8 milligrams of CBD. The lower-dose group received 9.9 milligrams of each cannabinoid, while the control group received placebo. Researchers then followed the patients for 24 hours and measured total morphine use along with pain levels while patients were resting and moving.
The high-dose group produced the most striking result. Average morphine consumption fell to 17.4 milligrams compared with 33.2 milligrams in the placebo group. The approximately 15.8-milligram absolute difference translates into a reduction of roughly 47.6 percent. Statistical analysis found the difference significant. The lower cannabinoid dose did not produce the same clearly demonstrated opioid-sparing result, suggesting that the effect seen in this experiment may depend on reaching a sufficiently strong cannabinoid dose rather than simply exposing patients to small amounts of THC and CBD.
Patients Used Less Morphine Without Reporting More Pain
Reducing opioid consumption is only useful if patients do not suffer significantly greater pain as a result. That makes the trial’s second major finding particularly important. Average pain scores remained similar across the placebo, low-dose and high-dose cannabinoid groups. On the study’s visual analog scale, average scores were approximately 5.1 for placebo, 5.5 for the low-dose cannabinoid group and 5.4 for the high-dose group. Researchers found no statistically significant difference among the three.
That creates an intriguing clinical interpretation. The high-dose cannabinoid group did not necessarily report dramatically lower pain than placebo, but those patients maintained approximately the same level of pain while requesting much less morphine. In an opioid-sparing strategy, that can be a meaningful outcome. The goal is not always for the additional medicine to eliminate pain by itself. An adjunct treatment can be useful if it allows clinicians to lower the amount of opioid required to produce an acceptable level of analgesia.
Why Reducing Morphine Exposure Matters
Morphine remains an important and effective medicine for severe acute pain, but opioid therapy carries significant risks. Common short-term effects include nausea, vomiting, constipation, sedation and itching. Higher doses can suppress breathing, particularly when opioids are combined with alcohol, sedatives or other central nervous system depressants. Repeated or prolonged exposure can also produce tolerance and physical dependence, while some patients eventually develop opioid use disorder.
Reducing the amount of opioid required for effective pain relief is therefore a major goal of modern pain medicine. Hospitals increasingly use multimodal analgesia, combining several medications or treatment approaches that act through different biological pathways. Acetaminophen, nonsteroidal anti-inflammatory drugs, local anesthetics, nerve blocks and other medications can all reduce opioid requirements in certain situations. Cannabinoids have long been proposed as another potential component of this strategy because the endocannabinoid and opioid systems interact at several levels of the nervous system.
THC and Morphine Affect Different but Interacting Pain Systems
THC primarily produces its well-known effects through CB1 cannabinoid receptors located throughout the brain, spinal cord and peripheral nervous system. These receptors influence the processing of pain signals, sensory perception and the emotional response to painful experiences. Morphine works mainly through mu-opioid receptors, another receptor system that strongly regulates pain. Because cannabinoid and opioid receptors are found in overlapping regions of the nervous system, researchers have investigated whether activating both systems can produce stronger analgesia than using either one alone.
Animal research has provided particularly compelling evidence for this possibility. Suzanne Nielsen and colleagues published an updated systematic review and meta-analysis in Neuropsychopharmacology in 2022 examining opioid-sparing effects of cannabinoids. Across seven preclinical studies, the median effective dose of morphine needed to produce pain relief was approximately 3.5 times lower when morphine was administered together with THC than when morphine was given by itself. That result suggested substantial biological synergy, although translating effects from laboratory animals into human patients has proven difficult.
Earlier Human Trials Produced Much Less Convincing Evidence
The same Nielsen review showed why the new 2026 trial is important. Although animal studies strongly supported an opioid-sparing interaction, higher-quality human trials had generally failed to demonstrate a reliable reduction in opioid consumption. Three randomized acute-pain studies included in the review found no convincing opioid-sparing effect, and a meta-analysis of four randomized studies involving cancer patients found no significant reduction in opioid dose when cannabinoid medicines were added.
Observational studies produced far more optimistic results. Across several studies, large percentages of medical cannabis patients reported reducing or stopping prescription opioid use after beginning cannabis treatment. Nielsen and colleagues calculated that approximately 39 percent of participants in observational studies reported stopping opioids, while about 85 percent reported some reduction. However, those studies were highly variable and vulnerable to self-selection, expectations and other biases. Patients who believe cannabis is helping may intentionally reduce opioids, and researchers cannot always determine whether comparable reductions would have occurred in a placebo group. The new Hadassah trial therefore carries additional weight because opioid use was randomized, controlled and measured directly.
A 2003 THC and Morphine Trial Found Only Limited Synergy
Researchers have been examining the interaction between THC and morphine in humans for more than two decades. A randomized double-blind crossover study led by Myrtha Naef and published in the journal Pain in 2003 gave healthy volunteers THC, morphine, a combination of the two or placebo before exposing them to controlled experimental pain tests involving heat, cold, pressure and electrical stimulation.
THC alone did not reliably reduce pain and even increased sensitivity in some tests. Combining THC with morphine produced a slight additive analgesic effect during electrical stimulation but did not consistently outperform morphine across every pain measure. Side effects including sleepiness, euphoria, anxiety, confusion, nausea and dizziness were common. That study involved experimental pain in only 12 healthy volunteers, making it very different from the new trial involving patients experiencing severe real-world radicular pain. Even so, it helped establish that combining cannabinoids and opioids could produce complex effects rather than automatically generating stronger analgesia.
CBD May Influence the Combination Without Acting Like THC
The new formulation contained equal amounts of THC and CBD, making it impossible to attribute the opioid reduction entirely to THC. CBD has very different pharmacology from THC and does not produce the characteristic cannabis intoxication associated with strong CB1 receptor activation. Research into CBD as a direct pain treatment has generally produced mixed results, and recent systematic reviews have found little convincing evidence that purified CBD alone produces substantial pain relief in most chronic pain conditions.
CBD may nevertheless alter some of THC’s effects or act through additional targets involved in inflammation, pain processing and neurotransmitter signaling. The formulation used in the new study also contained terpenes, meaning researchers were evaluating a standardized multi-component cannabis medicine rather than isolated THC. Because there was no THC-only or CBD-only comparison group, the study cannot determine whether CBD strengthened, weakened or had little effect on the morphine-sparing response.
New Research Suggests CBD Does Not Dramatically Alter Morphine Levels
One potential concern when combining cannabis compounds with opioids is drug interaction. CBD can affect enzymes responsible for metabolizing many medications, raising the possibility that it could change blood concentrations of another drug rather than producing a genuinely complementary analgesic effect. A 2026 clinical pharmacology study examined whether CBD meaningfully altered morphine pharmacokinetics in healthy adults.
Researchers found that neither a single CBD dose nor seven days of CBD administration produced a clinically meaningful change in morphine exposure. Morphine concentrations increased slightly after repeated CBD treatment, but the change was not considered large enough to be clinically significant. That study does not prove every cannabinoid formulation can be safely combined with morphine, but it provides some reassurance that the new opioid-sparing finding is unlikely to be explained simply by CBD causing a dramatic increase in morphine blood levels.
Side Effects Included Short-Lived Hallucinations
Cannabinoid treatment was not free of side effects. Three participants experienced hallucinations: one in the high-dose group and two in the low-dose group. All episodes lasted less than one hour and resolved without medical intervention. No participant withdrew from the trial because of an adverse effect, and investigators reported no serious adverse events attributed to the cannabinoid treatment.
The presence of hallucinations nevertheless matters when considering how the treatment might be used clinically. Nearly 20 milligrams of THC administered sublingually is a substantial dose, particularly for someone with little or no cannabis tolerance. THC can also cause dizziness, sedation, anxiety, altered perception, impaired coordination and increases in heart rate. Combining those effects with morphine requires careful medical supervision because both drugs can impair alertness, even though THC does not typically suppress breathing in the same way opioids do.
The Study Does Not Mean Patients Should Replace Opioids With Cannabis
The trial tested cannabinoids as an addition to morphine, not as a substitute for medical care. Every participant still had access to patient-controlled intravenous morphine, and average consumption in the high-dose cannabis group remained 17.4 milligrams. The finding therefore supports an adjunctive strategy: cannabinoids may reduce how much opioid some patients need while allowing opioids to remain available when pain requires them.
The research also involved a very specific clinical situation—acute radicular pain severe enough to bring patients to an emergency department. Results cannot automatically be extended to postoperative pain, cancer pain, arthritis, headaches or long-term chronic pain. Different pain mechanisms respond differently to medication, and cannabinoid products also vary enormously in dose, formulation and route of administration.
The Small Trial Needs to Be Repeated
The greatest limitation is the study’s size. Sixty-nine participants were divided among three groups, leaving only 26 patients in the high-dose group responsible for the headline result. Morphine consumption also varied considerably between individuals, as shown by the relatively large standard deviations. A larger multicenter trial could determine whether the nearly 48 percent reduction remains when hundreds of patients are studied across different hospitals and populations.
The study was also conducted at a single medical center. The cannabinoid formulation was supplied by Bazelet Group, and several study authors were employees of the company. The researchers reported that statistical analysis was performed by an external statistician who was blinded to treatment identity, while physicians at Hadassah were responsible for the original trial design. Industry involvement does not invalidate the findings, but independent replication would strengthen confidence in the result.
A Significant New Piece of the Opioid-Sparing Puzzle
For years, cannabinoid research has produced a frustrating mismatch. Laboratory experiments repeatedly suggested that THC could substantially increase the analgesic effectiveness of opioids, while observational studies reported large reductions in prescription opioid use among cannabis patients. Randomized human trials, however, generally failed to confirm a strong opioid-sparing effect. The new radicular-pain study begins to close that gap.
A single sublingual dose containing 19.8 milligrams each of THC and CBD reduced average morphine use from 33.2 milligrams to 17.4 milligrams over 24 hours while patients reported comparable pain intensity. That does not establish cannabis as a replacement for morphine, nor does it prove the same effect will appear in every type of pain. It does provide one of the clearer randomized human demonstrations that a standardized cannabinoid formulation can meaningfully reduce opioid requirements under controlled medical conditions. If larger trials reproduce the result, THC-and-CBD medicines could eventually become another tool in multimodal pain care—helping clinicians preserve the powerful analgesic benefits of opioids while exposing patients to less of them.
