520048 research-article2014
ANP0010.1177/0004867413520048Australian & New Zealand Journal of PsychiatryShipton and Shipton
Viewpoint Australian & New Zealand Journal of Psychiatry 2014, Vol. 48(4) 310–313 DOI: 10.1177/0004867413520048
Should doctors be allowed to prescribe cannabinoids for pain in Australia and New Zealand?
© The Royal Australian and New Zealand College of Psychiatrists 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav anp.sagepub.com
Edward A Shipton and Elspeth E Shipton
Introduction Clarification is needed around the use of cannabis in chronic pain. In Australia and New Zealand, general practitioners are routinely faced with patients who smoke cannabis for ‘so called’ medicinal reasons. Criminal drug laws in all Australian States continue to prohibit the possession, cultivation and supply of cannabis – even for medical purposes. In Australia, a parliamentary committee is recommending that the New South Wales Government amend legislation to allow the medical use of cannabis by patients with a terminal illness and those who have moved from HIV infection to AIDS (Legislative Council, 2013). The recommendation, if adopted by the Government, will allow patients with specific medical conditions certified by their specialist treating medical practitioner to possess and use up to 15 grams of dry cannabis or the equivalent amount of other cannabis products and equipment (Legislative Council, 2013). The inquiry by the Legislative Council’s General Purpose Standing Committee No. 4 was established in November 2012 to examine the efficacy and safety of cannabis for medical purposes. The Committee believed that people who are at the end of their life and take measures to either relieve their severe pain or stimulate their appetite should not be criminalised (Legislative Council, 2013). The medicinal use of cannabis has been much debated in New Zealand. It
has been estimated that 13.4% of those between the ages of 16 and 64 years in New Zealand use cannabis (United Nations Office on Drugs and Crime, 2006). In New Zealand, the use of cannabis is governed by the Misuse of Drugs Act 1975. Unauthorised possession of any amount of cannabis is illegal. In 2006, Metiria Turei from the New Zealand Green Party proposed the ‘Misuse of Drugs (Medicinal Cannabis) Amendment Bill’, whereby cannabis would be allowed for medicinal use (New Zealand Parliament, 2009). The bill was defeated. Calls are being made for the legalisation of cannabis, citing its compassionate use for alleviation of a number of ailments. The Law Commission’s Issues Paper on ‘Controlling and Regulating Drugs’ recommends those suffering from chronic or debilitating illnesses be able to use cannabis under medical supervision, particularly where conventional treatment options have proven ineffective (Law Commission, 2010). Pressure is being placed on the judicial system to condone its medicinal use. In March 2012, Victoria Davis was discharged without conviction by Judge Tony Zohrab on charges of cultivating cannabis. She grew the plants to help her husband cope with phantom pain. The New Zealand Medical Association does not oppose partial decriminalisation of the use of small amounts for medical purposes, provided it can be shown that no harm would result. In New Zealand, all injured patients are covered by accident compensation
insurance. The Accident Compensation Corporation in New Zealand has been requested to fund synthetic cannabis (nabiximols or Sativex®) for chronic pain, where conventional treatments have failed or are not tolerated. At present, Sativex® is approved for use as an add-on treatment for symptom improvement in unresponsive patients with spasticity due to multiple sclerosis under strict medical supervision after ministerial approval has been granted. The types of synthetic cannabinoids used are shown in Table 1.
Is there evidence that cannabinoids are effective in pain? There is a paucity of well-designed studies evaluating medical cannabis for pain (Borgelt et al., 2013). Limitations of these studies include widely varying doses and dosage forms of medical cannabis, lack of validated criteria or assessment for some types of pain, lack of comparative trials for various formulations and routes of administration, and small study populations
Department of Anaesthesia, University of Otago, Christchurch, Christchurch, New Zealand Corresponding author: Edward A Shipton, Department of Anaesthesia, University of Otago, Christchurch, PO Box 4345, Christchurch 8001, New Zealand. Email: [email protected]
Australian & New Zealand Journal of Psychiatry, 48(4) Downloaded from anp.sagepub.com at QUEENS UNIV LIBRARIES on March 10, 2015
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Shipton and Shipton Table 1. Synthetic cannabinoids and their composition. Synthetic cannabinoids
Composition
Nabiximols (Sativex®)
An oromucosal spray containing 2.7 mg of delta-9tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD)
Dronabinol (Marinol®)
An oral capsule of 2.5 mg of delta-9tetrahydrocannabinol (THC)
Nabilone (Cesamet®)
A delta-9-tetrahydrocannabinol (THC) analogue
(Borgelt et al., 2013). Hence, a cautious approach is needed. One systematic review has suggested cannabis to be moderately efficacious for chronic pain; its beneficial effects may, however, be offset by potentially serious harms (Martin-Sanchez et al., 2009). Another systematic review suggested that overall cannabinoids were safe and modestly effective in neuropathic pain (Lynch and Campbell, 2011).
Neuropathic pain Trials indicate that smoked cannabis or cannabis extract tetrahydrocannabinol (THC) / cannabidiol (CBD) can be effective for several different types of pain, primarily neuropathic pain (Borgelt et al., 2013). Seven short-term, placebocontrolled trials have suggested a slight to moderate reduction of neuropathic pain with nabiximols in patients with multiple sclerosis, advanced cancer, rheumatoid arthritis and mixed neuropathies with improved sleep (Podda and Constantinescum, 2012). In a double-blinded, placebo-controlled, crossover study, Wilsey et al. (2008) demonstrated an analgesic response to smoking cannabis (p = 0.016) in neuropathic pain. In chemotherapy-induced neuropathic pain, a recent pilot study supports the notion that it is worthwhile to study nabiximols in a full randomised, placebocontrolled trial (Lynch et al., 2013). Ware et al. (2010) studied patients with post-traumatic neuropathic pain. The daily pain intensity was significantly lower for those smoking 9.4% THC compared to placebo. Small limited studies have examined
the efficacy of smoked cannabis for neuropathic pain (Wilsey et al., 2008). A recent systematic review found that despite some jurisdictions making allowances for the ‘medical’ use of marijuana by patients with HIV/AIDS, evidence for the efficacy and safety of cannabis and cannabinoids in this setting is lacking (Lutge et al., 2013).
Other painful conditions Nabilone may be effective for pain related to fibromyalgia but also has not been widely studied (Borgelt et al., 2013). Oral THC (dronabinol) does not appear to be as effective as nabiximols for pain, but has not been widely studied in different pain conditions (Borgelt et al., 2013).
Adverse effects (Table 2) Cannabinoids present no risk for lethal overdose or end-organ failure. Reported adverse effects are typically not serious. In a systematic review of the use of cannabinoids in pain (Lynch and Campbell, 2011), the most common adverse events were sedation, dizziness, dry mouth, nausea, and disturbances in concentration. However, the psychoactive adverse effects poor co-ordination, ataxia, paranoid thinking, agitation, dissociation, euphoria and dysphoria were noted as well (Lynch and Campbell, 2011). In general, impairments in memory and cognition occur (Borgelt et al., 2013).
Psychiatric adverse effects Available data show that heavy cannabis use in adolescence increases the risk of
developing psychiatric disorders. In Australia, the use of cannabis is common in young people seeking mental healthcare. In a 10-year Australian follow-up, adolescents who used cannabis occasionally were found to be at higher risk of later drug abuse and educational problems (Degenhardt et al., 2010). There is an increased risk of developing schizophrenia with adolescent use (Borgelt et al., 2013). A recent metaanalysis has provided evidence for a relationship between cannabis use and earlier onset of psychotic illness (Large et al., 2011). Chronic regular cannabis use can produce a dependence syndrome in one in 10 users (Hall and Degenhardt, 2013).
Cognitive functioning Acute exposure to cannabinoids produces modest transient declines in cognitive performance. Heavy prolonged cannabis exposure may be associated with deficits in memory, sustained attention and executive functioning (D’Souza et al., 2009). Care is needed when prescribing medical cannabis for chronic pain, especially when learning and memory are integral to a patient’s work. Driving and the operation of dangerous equipment would need to be limited. There is a near doubling of risk of a driver being involved in a vehicle collision resulting in serious injury or death after ingestion of cannabis in the previous 3 hours (Asbridge et al., 2012).
Cardiovascular adverse effects Various reports have associated cannabis with cardiac arrhythmias, coronary insufficiency, myocardial infarction, and postural hypotension; caution is warranted for its use in patients with cardiovascular disease (Leung, 2011).
Other adverse effects A large Australian study of over 24,000 birthing women showed the use of cannabis in pregnancy to be associated with an increased risk of adverse birth
Australian & New Zealand Journal of Psychiatry, 48(4)
Downloaded from anp.sagepub.com at QUEENS UNIV LIBRARIES on March 10, 2015
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ANZJP Perspectives
Table 2. Adverse effects of cannabinoids (Borgelt et al., 2013; Lynch and Campbell, 2011; Wang et al., 2008). Common adverse effects
Less common adverse effects
Dizziness
Poor co-ordination
Sedation
Ataxia
Dry mouth
Paranoid thinking
Nausea
Agitation
Impairments in memory and cognition
Dissociation
Disturbances in concentration
Euphoria and dysphoria
Chronic bronchitis, impaired respiratory function
With cardiovascular disease, cannabis is associated with cardiac arrhythmias, coronary insufficiency, myocardial infarction, and postural hypotension. With adolescent use, there is an increased risk of developing schizophrenia, and impaired educational attainment.
Table 3. Guidance to doctors about cannabinoids. Use only in those patients who might benefit from their use – nabiximols are effective primarily for neuropathic pain Consider only when treatment failure with standard therapy has occurred or where other analgesic medications are not tolerated Only the oral and spray forms should be used Exercise extreme caution in patients with a history of cardiovascular disease, with mental disorders and in adolescents Adequately monitor and closely survey patients for the prevention of addiction Regular review is needed Dispensed medical prescribing of cannabis and nabiximols should be submitted to a national database (if available)
outcomes (Hayatbakhsh et al., 2012). Smoking cannabis is associated with decreasing pulmonary function, and may increase the risk of lung cancer in young adults. Other safety concerns in other countries are accidental paediatric ingestions and lack of safety packaging for medical cannabis formulations (Borgelt et al., 2013).
Is there evidence of efficacy over other medications or where these have failed? Cannabinoids in general do not offer advantages over current analgesics.
Should medical cannabinoids be used at all (Table 3)? Medical cannabinoids appear to have some limited benefits for patients with certain painful conditions, such as those with neuropathic pain from different causes (such as multiple sclerosis). Opioid addiction is a common adverse effect of extended opioid use by chronic pain sufferers. Research suggests that the biological actions of the cannabinoids might prove useful in reducing this opioid dependence. Patients in a palliative care setting who are currently on long-term opioids could potentially be treated with a combination using a lower dose of opioids.
Valid concerns However, there are a number of valid concerns. One is the unfavourable and somewhat variable adverse effect profile when used in different formulations as a medicinal product (such as inhalation from smoking) (Borgelt et al., 2013). To avoid the risks of smoking cannabis, an oral preparation of THC (dronabinol, a partial agonist at the CB1 receptors, marketed as Marinol®), an oral synthetic analogue of THC (nabilone, marketed as Cesamet®), and an oromucosal spray combining THC and CBD in a 1:1 mixture (nabiximols, marketed as Sativex®) have been developed (Table 1). The method of delivery and patient individuality cause great variability in its effect. There remains a lack of quality control of formulations used (Borgelt et al., 2013). Only the oral and spray forms should be used. There is a mandatory need for adequate monitoring and close surveillance of patients for the prevention of addiction (Borgelt et al., 2013). In addition, training and education should be made available to prescribers. Extreme caution should be exercised in the use of cannabinoids in patients with a history of cardiovascular disease or mental disorders and in adolescents (Borgelt et al., 2013). A national database should be set up in future to monitor information about the dispensed medical prescribing of cannabis and nabiximols, similar to data sources that collect information about the dispensed prescribing of opioid medications.
Conclusion The use of cannabinoids is highly topical in the medical world at present; it is particularly relevant to psychiatrists, with the debate being on the vulnerability of the adolescent brain towards cannabinoid exposure. There is renewed public interest and increased political pressure in Australia and New Zealand to allow the medicinal
Australian & New Zealand Journal of Psychiatry, 48(4) Downloaded from anp.sagepub.com at QUEENS UNIV LIBRARIES on March 10, 2015
313
Shipton and Shipton use of either smoked cannabis and/or cannabis extracts such as nabiximols (Sativex®). Given its legal status, the need for more efficacy data, and its unknown safety and tolerability profile, medical cannabis should be considered only for painful conditions when treatment failure with standard therapy has occurred or where other analgesic medications are not tolerated (Borgelt et al., 2013). Cannabinoids should only be used in those patients who might benefit from their use, such as those with neuropathic pain from various causes (including multiple sclerosis). Subject to all these provisos, there is a case to be made for medical cannabinoids to be legally available on a limited basis to patients with specific pain conditions. This must be carried out under strict qualified medical supervision. In New Zealand, this would entail a change in legislation. Future cannabinoid research should focus on formulations without the THC component resulting in analgesia and without psychiatric adverse effects. These new formulations would not further the cause of those desiring legislation change for street cannabis. High-quality studies (with large study populations and long-term exposure) are needed to determine the appropriate uses of medical cannabinoids. Formulations and dosages require standardisation. Given the prevalence of chronic pain, more research into the cannabinoids should be funded. Keywords Cannabinoids, pain relief
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Declaration of interest The authors report no financial disclosures, grant support, or conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Asbridge M, Hayden JA and Cartwright JL (2012) Acute cannabis consumption and motor vehicle collision risk: Systematic review of observational studies and meta-analysis. British Medical Journal 344: e536. Borgelt LM, Franson KL, Nussbaum AM, et al. (2013) The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 33: 195–209. Degenhardt L, Coffey C, Carlin JB, et al. (2010) Outcomes of occasional cannabis use in adolescence: 10-year follow-up study in Victoria, Australia. British Journal of Psychiatry 196: 290–295. D’Souza DC, Sewell RA and Ranganathan M (2009) Cannabis and psychosis/schizophrenia: Human studies. European Archives of Psychiatry and Clinical Neuroscience 259: 413–431. Hall W and Degenhardt L (2013) The adverse health effects of chronic cannabis use. Drug Testing and Analysis. Epub ahead of print 8 Jul 2013. DOI: 10.1002/dta.1506. Hayatbakhsh MR, Flenady VJ, Gibbons KS, et al. (2012) Birth outcomes associated with cannabis use before and during pregnancy. Pediatric Research 71: 215–219. Large M, Sharma S, Compton MT, et al. (2011) Cannabis use and earlier onset of psychosis: A systematic meta-analysis. Archives of General Psychiatry 68: 555–661. Law Commission (2010) Controlling and Regulating Drugs. Issues Paper 16 (NZLC IP16): pp. 21. Legislative Council – General Purpose Standing Committee No. 4 (2013) Parliamentary committee recommends reforms to allow medical use of cannabis by people with terminal illness
and AIDS. Media Release. 15 May. Sydney: NSW Parliament. Leung L (2011) Cannabis and its derivatives: Review of medical use. Journal of the American Board of Family Medicine 24: 452–462. Lutge EE, Gray A and Siegfried N (2013) The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS. The Cochrane Database of Systematic Reviews 4: CD005175. Lynch ME and Campbell F (2011) Cannabinoids for treatment of chronic non-cancer pain; A systematic review of randomized trials. British Journal of Clinical Pharmacology 72: 735–744. Lynch ME, Cesar-Rittenberg P and Hohmann AG (2013) A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. Journal of Pain and Symptom Management. Epub ahead of print 4 Jun 2013. DOI: 10.1016/j.jpainsymman.2013.02.018. Martin-Sanchez E, Furukawa TA, Taylor J, et al. (2009) Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Medicine 10: 1353–1368. New Zealand Parliament (2009) Misuse of Drugs (Medicinal Cannabis) Amendment Bill. Available at: http://www.parliament.nz/en-nz/pb/legislation/ bills/00DBHOH_BILL7386_1/misuse-of-drugsmedicinal-cannabis-amendment-bill (accessed 8 December 2012). Podda G and Constantinescum CS (2012) Nabiximols in the treatment of spasticity, pain and urinary symptoms due to multiple sclerosis. Expert Opinion on Biological Therapy 12: 1517–1531. United Nations Office on Drugs and Crime (2006) World Drug Report. New York, NY / Geneva, Switzerland: United Nations Publications. Wang T, Collet JP, Shapiro S, et al. (2008) Adverse effects of medical cannabinoids: A systematic review. Canadian Medical Association Journal 178: 1669–1678. Ware MA, Wang T, Shapiro S, et al. (2010) Smoked cannabis for chronic neuropathic pain: A randomized controlled trial. Canadian Medical Association Journal 182: E694–E701. Wilsey B, Marcotte T, Tsodikov A, et al. (2008) A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. Journal of Pain 9: 506–521.
Australian & New Zealand Journal of Psychiatry, 48(4)
Downloaded from anp.sagepub.com at QUEENS UNIV LIBRARIES on March 10, 2015
ANP0010.1177/0004867413520048Australian & New Zealand Journal of PsychiatryShipton and Shipton
Viewpoint Australian & New Zealand Journal of Psychiatry 2014, Vol. 48(4) 310–313 DOI: 10.1177/0004867413520048
Should doctors be allowed to prescribe cannabinoids for pain in Australia and New Zealand?
© The Royal Australian and New Zealand College of Psychiatrists 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav anp.sagepub.com
Edward A Shipton and Elspeth E Shipton
Introduction Clarification is needed around the use of cannabis in chronic pain. In Australia and New Zealand, general practitioners are routinely faced with patients who smoke cannabis for ‘so called’ medicinal reasons. Criminal drug laws in all Australian States continue to prohibit the possession, cultivation and supply of cannabis – even for medical purposes. In Australia, a parliamentary committee is recommending that the New South Wales Government amend legislation to allow the medical use of cannabis by patients with a terminal illness and those who have moved from HIV infection to AIDS (Legislative Council, 2013). The recommendation, if adopted by the Government, will allow patients with specific medical conditions certified by their specialist treating medical practitioner to possess and use up to 15 grams of dry cannabis or the equivalent amount of other cannabis products and equipment (Legislative Council, 2013). The inquiry by the Legislative Council’s General Purpose Standing Committee No. 4 was established in November 2012 to examine the efficacy and safety of cannabis for medical purposes. The Committee believed that people who are at the end of their life and take measures to either relieve their severe pain or stimulate their appetite should not be criminalised (Legislative Council, 2013). The medicinal use of cannabis has been much debated in New Zealand. It
has been estimated that 13.4% of those between the ages of 16 and 64 years in New Zealand use cannabis (United Nations Office on Drugs and Crime, 2006). In New Zealand, the use of cannabis is governed by the Misuse of Drugs Act 1975. Unauthorised possession of any amount of cannabis is illegal. In 2006, Metiria Turei from the New Zealand Green Party proposed the ‘Misuse of Drugs (Medicinal Cannabis) Amendment Bill’, whereby cannabis would be allowed for medicinal use (New Zealand Parliament, 2009). The bill was defeated. Calls are being made for the legalisation of cannabis, citing its compassionate use for alleviation of a number of ailments. The Law Commission’s Issues Paper on ‘Controlling and Regulating Drugs’ recommends those suffering from chronic or debilitating illnesses be able to use cannabis under medical supervision, particularly where conventional treatment options have proven ineffective (Law Commission, 2010). Pressure is being placed on the judicial system to condone its medicinal use. In March 2012, Victoria Davis was discharged without conviction by Judge Tony Zohrab on charges of cultivating cannabis. She grew the plants to help her husband cope with phantom pain. The New Zealand Medical Association does not oppose partial decriminalisation of the use of small amounts for medical purposes, provided it can be shown that no harm would result. In New Zealand, all injured patients are covered by accident compensation
insurance. The Accident Compensation Corporation in New Zealand has been requested to fund synthetic cannabis (nabiximols or Sativex®) for chronic pain, where conventional treatments have failed or are not tolerated. At present, Sativex® is approved for use as an add-on treatment for symptom improvement in unresponsive patients with spasticity due to multiple sclerosis under strict medical supervision after ministerial approval has been granted. The types of synthetic cannabinoids used are shown in Table 1.
Is there evidence that cannabinoids are effective in pain? There is a paucity of well-designed studies evaluating medical cannabis for pain (Borgelt et al., 2013). Limitations of these studies include widely varying doses and dosage forms of medical cannabis, lack of validated criteria or assessment for some types of pain, lack of comparative trials for various formulations and routes of administration, and small study populations
Department of Anaesthesia, University of Otago, Christchurch, Christchurch, New Zealand Corresponding author: Edward A Shipton, Department of Anaesthesia, University of Otago, Christchurch, PO Box 4345, Christchurch 8001, New Zealand. Email: [email protected]
Australian & New Zealand Journal of Psychiatry, 48(4) Downloaded from anp.sagepub.com at QUEENS UNIV LIBRARIES on March 10, 2015
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Shipton and Shipton Table 1. Synthetic cannabinoids and their composition. Synthetic cannabinoids
Composition
Nabiximols (Sativex®)
An oromucosal spray containing 2.7 mg of delta-9tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD)
Dronabinol (Marinol®)
An oral capsule of 2.5 mg of delta-9tetrahydrocannabinol (THC)
Nabilone (Cesamet®)
A delta-9-tetrahydrocannabinol (THC) analogue
(Borgelt et al., 2013). Hence, a cautious approach is needed. One systematic review has suggested cannabis to be moderately efficacious for chronic pain; its beneficial effects may, however, be offset by potentially serious harms (Martin-Sanchez et al., 2009). Another systematic review suggested that overall cannabinoids were safe and modestly effective in neuropathic pain (Lynch and Campbell, 2011).
Neuropathic pain Trials indicate that smoked cannabis or cannabis extract tetrahydrocannabinol (THC) / cannabidiol (CBD) can be effective for several different types of pain, primarily neuropathic pain (Borgelt et al., 2013). Seven short-term, placebocontrolled trials have suggested a slight to moderate reduction of neuropathic pain with nabiximols in patients with multiple sclerosis, advanced cancer, rheumatoid arthritis and mixed neuropathies with improved sleep (Podda and Constantinescum, 2012). In a double-blinded, placebo-controlled, crossover study, Wilsey et al. (2008) demonstrated an analgesic response to smoking cannabis (p = 0.016) in neuropathic pain. In chemotherapy-induced neuropathic pain, a recent pilot study supports the notion that it is worthwhile to study nabiximols in a full randomised, placebocontrolled trial (Lynch et al., 2013). Ware et al. (2010) studied patients with post-traumatic neuropathic pain. The daily pain intensity was significantly lower for those smoking 9.4% THC compared to placebo. Small limited studies have examined
the efficacy of smoked cannabis for neuropathic pain (Wilsey et al., 2008). A recent systematic review found that despite some jurisdictions making allowances for the ‘medical’ use of marijuana by patients with HIV/AIDS, evidence for the efficacy and safety of cannabis and cannabinoids in this setting is lacking (Lutge et al., 2013).
Other painful conditions Nabilone may be effective for pain related to fibromyalgia but also has not been widely studied (Borgelt et al., 2013). Oral THC (dronabinol) does not appear to be as effective as nabiximols for pain, but has not been widely studied in different pain conditions (Borgelt et al., 2013).
Adverse effects (Table 2) Cannabinoids present no risk for lethal overdose or end-organ failure. Reported adverse effects are typically not serious. In a systematic review of the use of cannabinoids in pain (Lynch and Campbell, 2011), the most common adverse events were sedation, dizziness, dry mouth, nausea, and disturbances in concentration. However, the psychoactive adverse effects poor co-ordination, ataxia, paranoid thinking, agitation, dissociation, euphoria and dysphoria were noted as well (Lynch and Campbell, 2011). In general, impairments in memory and cognition occur (Borgelt et al., 2013).
Psychiatric adverse effects Available data show that heavy cannabis use in adolescence increases the risk of
developing psychiatric disorders. In Australia, the use of cannabis is common in young people seeking mental healthcare. In a 10-year Australian follow-up, adolescents who used cannabis occasionally were found to be at higher risk of later drug abuse and educational problems (Degenhardt et al., 2010). There is an increased risk of developing schizophrenia with adolescent use (Borgelt et al., 2013). A recent metaanalysis has provided evidence for a relationship between cannabis use and earlier onset of psychotic illness (Large et al., 2011). Chronic regular cannabis use can produce a dependence syndrome in one in 10 users (Hall and Degenhardt, 2013).
Cognitive functioning Acute exposure to cannabinoids produces modest transient declines in cognitive performance. Heavy prolonged cannabis exposure may be associated with deficits in memory, sustained attention and executive functioning (D’Souza et al., 2009). Care is needed when prescribing medical cannabis for chronic pain, especially when learning and memory are integral to a patient’s work. Driving and the operation of dangerous equipment would need to be limited. There is a near doubling of risk of a driver being involved in a vehicle collision resulting in serious injury or death after ingestion of cannabis in the previous 3 hours (Asbridge et al., 2012).
Cardiovascular adverse effects Various reports have associated cannabis with cardiac arrhythmias, coronary insufficiency, myocardial infarction, and postural hypotension; caution is warranted for its use in patients with cardiovascular disease (Leung, 2011).
Other adverse effects A large Australian study of over 24,000 birthing women showed the use of cannabis in pregnancy to be associated with an increased risk of adverse birth
Australian & New Zealand Journal of Psychiatry, 48(4)
Downloaded from anp.sagepub.com at QUEENS UNIV LIBRARIES on March 10, 2015
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ANZJP Perspectives
Table 2. Adverse effects of cannabinoids (Borgelt et al., 2013; Lynch and Campbell, 2011; Wang et al., 2008). Common adverse effects
Less common adverse effects
Dizziness
Poor co-ordination
Sedation
Ataxia
Dry mouth
Paranoid thinking
Nausea
Agitation
Impairments in memory and cognition
Dissociation
Disturbances in concentration
Euphoria and dysphoria
Chronic bronchitis, impaired respiratory function
With cardiovascular disease, cannabis is associated with cardiac arrhythmias, coronary insufficiency, myocardial infarction, and postural hypotension. With adolescent use, there is an increased risk of developing schizophrenia, and impaired educational attainment.
Table 3. Guidance to doctors about cannabinoids. Use only in those patients who might benefit from their use – nabiximols are effective primarily for neuropathic pain Consider only when treatment failure with standard therapy has occurred or where other analgesic medications are not tolerated Only the oral and spray forms should be used Exercise extreme caution in patients with a history of cardiovascular disease, with mental disorders and in adolescents Adequately monitor and closely survey patients for the prevention of addiction Regular review is needed Dispensed medical prescribing of cannabis and nabiximols should be submitted to a national database (if available)
outcomes (Hayatbakhsh et al., 2012). Smoking cannabis is associated with decreasing pulmonary function, and may increase the risk of lung cancer in young adults. Other safety concerns in other countries are accidental paediatric ingestions and lack of safety packaging for medical cannabis formulations (Borgelt et al., 2013).
Is there evidence of efficacy over other medications or where these have failed? Cannabinoids in general do not offer advantages over current analgesics.
Should medical cannabinoids be used at all (Table 3)? Medical cannabinoids appear to have some limited benefits for patients with certain painful conditions, such as those with neuropathic pain from different causes (such as multiple sclerosis). Opioid addiction is a common adverse effect of extended opioid use by chronic pain sufferers. Research suggests that the biological actions of the cannabinoids might prove useful in reducing this opioid dependence. Patients in a palliative care setting who are currently on long-term opioids could potentially be treated with a combination using a lower dose of opioids.
Valid concerns However, there are a number of valid concerns. One is the unfavourable and somewhat variable adverse effect profile when used in different formulations as a medicinal product (such as inhalation from smoking) (Borgelt et al., 2013). To avoid the risks of smoking cannabis, an oral preparation of THC (dronabinol, a partial agonist at the CB1 receptors, marketed as Marinol®), an oral synthetic analogue of THC (nabilone, marketed as Cesamet®), and an oromucosal spray combining THC and CBD in a 1:1 mixture (nabiximols, marketed as Sativex®) have been developed (Table 1). The method of delivery and patient individuality cause great variability in its effect. There remains a lack of quality control of formulations used (Borgelt et al., 2013). Only the oral and spray forms should be used. There is a mandatory need for adequate monitoring and close surveillance of patients for the prevention of addiction (Borgelt et al., 2013). In addition, training and education should be made available to prescribers. Extreme caution should be exercised in the use of cannabinoids in patients with a history of cardiovascular disease or mental disorders and in adolescents (Borgelt et al., 2013). A national database should be set up in future to monitor information about the dispensed medical prescribing of cannabis and nabiximols, similar to data sources that collect information about the dispensed prescribing of opioid medications.
Conclusion The use of cannabinoids is highly topical in the medical world at present; it is particularly relevant to psychiatrists, with the debate being on the vulnerability of the adolescent brain towards cannabinoid exposure. There is renewed public interest and increased political pressure in Australia and New Zealand to allow the medicinal
Australian & New Zealand Journal of Psychiatry, 48(4) Downloaded from anp.sagepub.com at QUEENS UNIV LIBRARIES on March 10, 2015
313
Shipton and Shipton use of either smoked cannabis and/or cannabis extracts such as nabiximols (Sativex®). Given its legal status, the need for more efficacy data, and its unknown safety and tolerability profile, medical cannabis should be considered only for painful conditions when treatment failure with standard therapy has occurred or where other analgesic medications are not tolerated (Borgelt et al., 2013). Cannabinoids should only be used in those patients who might benefit from their use, such as those with neuropathic pain from various causes (including multiple sclerosis). Subject to all these provisos, there is a case to be made for medical cannabinoids to be legally available on a limited basis to patients with specific pain conditions. This must be carried out under strict qualified medical supervision. In New Zealand, this would entail a change in legislation. Future cannabinoid research should focus on formulations without the THC component resulting in analgesia and without psychiatric adverse effects. These new formulations would not further the cause of those desiring legislation change for street cannabis. High-quality studies (with large study populations and long-term exposure) are needed to determine the appropriate uses of medical cannabinoids. Formulations and dosages require standardisation. Given the prevalence of chronic pain, more research into the cannabinoids should be funded. Keywords Cannabinoids, pain relief
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Declaration of interest The authors report no financial disclosures, grant support, or conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Asbridge M, Hayden JA and Cartwright JL (2012) Acute cannabis consumption and motor vehicle collision risk: Systematic review of observational studies and meta-analysis. British Medical Journal 344: e536. Borgelt LM, Franson KL, Nussbaum AM, et al. (2013) The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 33: 195–209. Degenhardt L, Coffey C, Carlin JB, et al. (2010) Outcomes of occasional cannabis use in adolescence: 10-year follow-up study in Victoria, Australia. British Journal of Psychiatry 196: 290–295. D’Souza DC, Sewell RA and Ranganathan M (2009) Cannabis and psychosis/schizophrenia: Human studies. European Archives of Psychiatry and Clinical Neuroscience 259: 413–431. Hall W and Degenhardt L (2013) The adverse health effects of chronic cannabis use. Drug Testing and Analysis. Epub ahead of print 8 Jul 2013. DOI: 10.1002/dta.1506. Hayatbakhsh MR, Flenady VJ, Gibbons KS, et al. (2012) Birth outcomes associated with cannabis use before and during pregnancy. Pediatric Research 71: 215–219. Large M, Sharma S, Compton MT, et al. (2011) Cannabis use and earlier onset of psychosis: A systematic meta-analysis. Archives of General Psychiatry 68: 555–661. Law Commission (2010) Controlling and Regulating Drugs. Issues Paper 16 (NZLC IP16): pp. 21. Legislative Council – General Purpose Standing Committee No. 4 (2013) Parliamentary committee recommends reforms to allow medical use of cannabis by people with terminal illness
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