Opioids vs Medicinal Cannabis for Pain

Understanding the Landscape: Pain in Australia

Chronic pain affects millions of Australians and is associated with reduced quality of life, disability, and considerable socioeconomic burden . For many, finding effective relief while minimising risks is an ongoing challenge.

Key facts about pain management:

• Chronic non-cancer pain impacts approximately 20% of the global population 

• 30% to 40% of people with chronic pain also experience depression 

• People with chronic pain have two to three times higher suicide risk than the general population 

• The majority of survey respondents (85%) support the use of medicinal cannabis for pain management 

 How Opioids Work for Pain

Opioids have long been considered the cornerstone of pain management protocols for moderate to severe pain . These medications work by binding to opioid receptors in the brain and spinal cord, reducing the perception of pain.

Mechanism of action:

• Act on μ-, κ-, and δ-opioid receptors in the presynaptic membrane

• Decrease calcium influx in presynaptic membranes

• Increase potassium influx in postsynaptic membranes

• Change the perception of pain in the brain while increasing pain threshold in the spinal cord 

Common opioids prescribed in Australia include:

• Oxycodone

• Morphine

• Codeine

• Fentanyl

• Tramadol

Moderate certainty evidence shows that opioids provide small improvements in pain, physical functioning, and sleep quality compared to placebo .

 How Medicinal Cannabis Works for Pain

Medicinal cannabis offers an alternative approach to pain modulation through the body’s endocannabinoid system.

Mechanism of action:

• Endocannabinoids are released by synapses to act on CB1 and CB2 receptors on presynaptic endings

• Decrease neurotransmitter release

• Activate descending inhibitory pain pathways

• Reduce postsynaptic sensitivity and alleviate neural inflammation

• Modulate CB1 receptors within central nociception processing areas

• Attenuate inflammation through CB2 receptor activation 

Key components:

• THC (delta-9-tetrahydrocannabinol) – The psychoactive component with pain-relieving properties

• CBD (cannabidiol) – Non-psychoactive component with anti-inflammatory effects 

Administration methods available by prescription:

• Oils and tinctures

• Capsules

• Dried flower for vaporisation (smoking is not supported by the TGA)

• Oral sprays

• Topicals

Low to moderate certainty evidence supports similar effects for cannabis versus placebo for pain relief .

 Head-to-Head: What the Research Shows

Comparative Effectiveness

A landmark 2024 systematic review and network meta-analysis published in BMJ Open examined 90 trials involving 22,028 patients to compare opioids and cannabis for chronic non-cancer pain .

Key findings:

Response Rates

A 2025 study published in the journal Pain comparing 440 patients using medical marijuana with 8,114 patients using prescription medications found:

• Medical marijuana group: 38.6% showed clinically meaningful improvements at 3 months (maintained at 6 months)

• Prescription medication group: 34.9% showed improvements at 3 months

• Odds ratio of 2.6 in favour of medical marijuana vs medication treatment (statistically significant) 

The researchers concluded that medical marijuana was comparatively more effective than prescription medications for treating chronic pain at 3 months .

The Opioid-Sparing Effect

One of the most significant findings in recent research is cannabis’s potential to reduce opioid consumption.

Australian Study (2025)

A longitudinal study published in Pain Management followed chronic pain patients over 12 months :

Patients who received cannabis also experienced greater improvements in depression, anxiety, insomnia, and disability compared to the control group .

Pittsburgh Study (2025)

Among 157 patients co-prescribed opioids and medical marijuana, there was a mean 39.3% decrease in morphine milligram equivalents over 6 months (statistically significant) .

These findings align with ecological studies from the US and Canada reporting significant overall declines in opioid prescriptions following cannabis legalisation .

Safety and Side Effects: Critical Considerations

Opioid Risks

Opioids are associated with significant safety concerns :

• Respiratory depression – Can lead to death (does not occur with cannabis) 

• Addiction and dependence – Opioid use disorder is a leading cause of drug-related deaths 

• Overdose risk – Fatal respiratory depression

• Constipation and miosis – May persist throughout treatment 

• Opioid-induced hyperalgesia – Increased sensitivity to pain

• Neonatal Opioid Withdrawal Syndrome (NOWS) – Risks in pregnancy 

• Withdrawal symptoms – Yawning, sweating, lacrimation, piloerection 

Cannabis Side Effects

Cannabis is not without its own adverse effects :

• Common: Drowsiness, dizziness, dry mouth

• Study dropout rates: 31% of patients receiving inhaled cannabis discontinued due to adverse effects (most notably headaches) 

• Cannabis Use Disorder (CUD): Affects approximately 10% of cannabis users worldwide 

• Adolescent risks: Leading cause of addiction in adolescents 

• Mental health concerns: Studies link cannabis use to increased risk for chronic psychosis and worse outcomes for people with existing psychosis 

• Drug interactions: THC and CBD can inhibit CYP2C9 (affecting warfarin metabolism) and compete with drugs like clopidogrel, digoxin, and loperamide 

Tolerability Comparison

Importantly, moderate certainty evidence shows that cannabis resulted in fewer discontinuations due to adverse events versus opioids (odds ratio 0.55, statistically significant) .

A Bedrocan-funded study noted: “The use of opioids is more dangerous than the use of cannabis. Using opioids can cause respiratory depression, which can lead to death. That is not the case with cannabis” .

Patient Perspectives and Preferences

A Painaustralia survey of 454 individuals revealed :

• 85% supported medicinal cannabis use for pain management

• Many preferred cannabis over opioids due to side-effects and risk of death associated with opioids

• Others had exhausted other possibilities for pain relief

• 62% obtained information about medicinal cannabis from friends or family

• 33% were not aware of any scientific research supporting medicinal cannabis for pain

• Only 24% knew they could access medicinal cannabis legally through the TGA Special Access Scheme with GP support

This highlights the critical need for clearer public education about both treatment options .

 Mental Health Considerations

The comorbidity between chronic pain and mental health conditions is well documented :

• 30-40% of chronic pain patients experience depression

• Two to three times higher suicide risk than general population

This makes the mental health effects of any pain treatment particularly important:

• Opioids: Associated with mood changes and dependence risks

• Cannabis: Studies have linked use to increased risk for chronic psychosis and worse outcomes for people with existing psychosis 

The Royal Australian and New Zealand College of Psychiatrists notes these concerns, emphasising that for a population as vulnerable as chronic pain patients, it would be “remiss not to be concerned about possible adverse outcomes” .

 Australian Context: Legal Access

Access Pathways

In Australia, medicinal cannabis is legal only with a valid prescription from a registered medical practitioner through :

• Special Access Scheme (SAS-B) – Individual patient approval (typically 24-48 hours)

• Authorised Prescriber (AP) Scheme – For ongoing treatment of specific patient groups

Important Considerations

Painaustralia emphasises: “There are few well-designed clinical studies which support the use of medicinal cannabis for chronic non-cancer pain. Without proper evidence, making medicinal cannabis more available could see millions of Australians living with chronic pain offered ‘false hope’ of a treatment option that has limited benefit” .

The Evidence Gap and Future Research

Despite growing interest, significant evidence gaps remain:

What we need:

• Direct comparisons of opioids versus cannabis in randomised trials 

• Long-term studies to inform benefits and harms 

• Research identifying which patients respond best to which treatment 

• Data on rare but serious harms 

• Randomised trials to establish opioid-substitution effects 

What’s happening:

• The Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE) received $2.5 million in NHMRC funding to coordinate research 

• Ongoing studies are examining safety and effectiveness

• The TGA continues to evaluate emerging evidence

 Making an Informed Decision

Questions to Discuss With Your Doctor

If you’re considering either treatment approach, ask your healthcare provider:

1. What is the evidence for this treatment for my specific condition?

2. What are the potential benefits and risks?

3. How will we monitor effectiveness and side effects?

4. What other treatment options should I consider?

5. If considering cannabis, do I meet the eligibility criteria for TGA approval?

Important Considerations