A Herbal Approach to the Treatment of Withdrawal from Opioid and Benzodiazepine Dependence

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1 A Herbal Approach to the Treatment of Withdrawal from Opioid and Benzodiazepine Dependence By Ally Hurcikova, 3rd yr. Lincoln University Published in Student Herbal Thymes Winter Edition 2014/2015 Drug addiction remains a widespread issue in the UK, affecting every strata of society and bringing with it considerable ill health and social problems. Historically, the phrase drug addiction has sparked connotations of illicit street drug use, but increasingly addiction is becoming medicalised with incidences of prescription drug abuse continually rising. The use of opioid painkillers and anxiolytic benzodiazepines is spiralling in contemporary society (MHRA, 2011). Despite this addiction is an area that is not often discussed in relation to herbal treatment. This report is intended as a study of the role that herbal medicine can play in the treatment of withdrawal from dependent use of opioids and benzodiazepines. These two classes of drugs are distinct, with different neuropharmacological actions and pathways, but both have a relatable depressant action on the nervous system and are often abused in conjunction with each other (Jones et al, 2012). A common picture now is what is termed polypharmacy, with users often combining heroin, alcohol, cannabis, benzodiazepines and other prescriptions (O Brien, 2007). Worryingly, despite withdrawal from one class exacerbating withdrawal symptoms from the other class, clinicians often prescribe benzodiazepines as part of a strategy for opioid withdrawal (de Wet et al, 2004:31). This report will group these two classes together broadly as anxiolytic central nervous system depressants, and approach herbal treatment for withdrawal in a similar way. Opioids and Benzodiazepines Opioid is a general term for any compound, synthetic or natural, that binds to opioid receptors in the central and peripheral nervous system and GIT. Commonly used opioids include Heroin, Opium, Morphine, Codeine, Tramadol, Pethidine, Oxycontin, and other derivates (Aldred, 2009:252). Opioids have a depressant action on the body, altering perception and response to pain. Morphine in the brain binds MOP-r (an opioid receptor) and relieves GABAergic inhibition of dopamingergic neurons. This leads to a flood of dopamine into the projection fields (Kreek et al, 2012:3389), creating feelings of pleasure and reward. The physiological effects of this class of drugs include: - Analgesia including euphoria and sedation

2 - Depression of vasomotor centre - Depression of respiration - Cough suppression - Decrease in urination - Smooth muscle contraction, with reduced motility of the GIT (Aldred, 2009:252). Benzodiazepines are a commonly prescribed class of sedative and anxiolytic medicine which include Diazepam, Lorazepam, Temazepam, Valium, Loprazolam, Clonazepam (patient.co.uk, 2013). They are used to control symptoms of anxiety and muscle spasm, without considerably impairing normal function of the patient (Page, 2002). Neuropharmacologically, benzodiazepines potentiate GABA transmission, calming patients, and acting on the limbic system to mediate feelings of emotional arousal (Aldred, 2009:265). For over 20 years, pharmaceutical prescribing advice has limited the duration of benzodiazepines to 2-4 weeks, in concern about the risk of dependence and withdrawal reactions (MHRA, 2011). In practice however, it is not uncommon to see individuals who have been taking Diazepam daily for a number of years. Continual use of both classes are also characterised by tolerance and dependence: an individual becomes physiologically accustomed to the drug and requires higher doses to achieve the same effect (Adrian & Hyg, 2003:1386). The body then requires the substance to function normally, dose reduction brings on withdrawal symptoms. Addiction is defined as: dependence on a substance, characterised by a) tolerance, b) preoccupation with obtaining and using the substance, c) use of the substance despite actual or potential adverse biopsychosocial consequences, d) repeated efforts to cut down or control the use, and e) withdrawal symptoms when the substance is removed (Rasmussen S, 2000:8). European research has indicated that the UK has the highest prevalence of problem drug use on the continent. This use applies to illegal street drugs as well as abuse of pharmaceuticals like Valium, Diazepam, Codeine and Tramadol. A 2011 report of the UK s National Treatment Agency and National Addiction Centre showed the use of benzodiazepines as anxiolytic drugs increased between 1991 and 2009, and over the counter sales of codeine-containing medicines has also increased since they were placed on the market in 2006 (MHRA, 2011). Focusing locally on Edinburgh, a study into the number of injecting heroin users in the period of 1992 to 1994 found an estimated 1770, which was then 8% per 1000 Edinburgh residents aged (Davies et al, 1999:117). To put this into a comparative European context, the Netherlands with its population of 16.6 million has 30,000 dependent heroin users, and Scotland has 52,000 despite having a population of less than a third

3 of Holland (Hay et al, 2005 cited in Egan, 2010). Britain also has among the highest numbers in Europe living in relative poverty, a factor closely correlated to substance abuse and addiction (Egan, 2010:186). Socioeconomic and Psychopathological Background of Addiction Any cursory scan of orthodox medical literature on addiction will reveal a heavy focus on neurobiology and genetics. Addiction is increasingly termed a brain disease (see Leshner, 1997). Accordingly, socioeconomic and psychopathological factors are all too often ignored in mainstream literature and related health and social policy recommendations. Dislocating addiction from its wider context ignores statistics that show a significant proportion of those with serious drugs problems are faced with greater socioeconomic disadvantage and inequality. They are also more closely correlated to disrupted childhoods, personal trauma, relationship breakdown, underachievement and unemployment (Buchanan, 2004 cited in Egan, 2010). The largest longitudinal study conducted on long term heroin users in Australia found high levels of psychological distress, with half of users having severely disabled mental health, and 90% been exposed to trauma. Over half of the women had been raped and men were more likely to have been exposed to violence than the general population (Darke et al, 2007:51). In England and Wales, between 1993 and 2006 drug related deaths were five times higher in the most deprived areas as compared with the least deprived. (Brock et al, 2008 cited in Egan, 2010:188). It is clear from only a few studies that addiction and social inequality in the UK continues to be a significant issue and one that isn t likely to diminish soon, particularly in the current climate of economic decline and unemployment; herbal medicine certainly can have a role to play. There is no cure or silver bullet for addiction and it is essential that a holistic approach to treatment and recovery does not ignore these factors. Every drug user is an individual, living through their own set of circumstances and experiences, understood best only by them. Pathophysiology of Dependent Opioid and Benzodiazepine Use Dependent use of either of these classes of drugs can bring with it various health problems. Chronic consumption of opioids or benzodiazepines is related to insomnia, depression, weight gain, worsening diet and general health decline (Erowid, 2010). It can also lead to significant liver damage, as the liver is responsible for removing lipophilic substances including morphine and heroin from plasma (Ilic et al, 2005:150). During bio-transformation of opioids and benzodiazepines, hepatocyte changes and liver damage can occur. Liver damage is particularly severe for chronic intravenous heroin users. In a study undertaken

4 into the autopsied livers of users who had been injecting heroin for over 10 years, 100% had hepatitis as a result of the long term hepatic morphological changes (Ilic et al, 2005:151). Intravenous drug use can also lead to injection site infections, collapsed or hardened veins, septicaemia and cardiovascular damage (Erowid, 2010). Opioid exposure alters the physiology of the kidneys, modifying urine output and sodium excretion, and affecting renal tubular sodium reabsorption (Kouros et al, 2010:135). Importantly however, physical recovery is possible. A longitudinal Australian study following addicts through recovery found that the mental health of the cohort was significantly worse than their physical health. After successful treatment, physical health returned to population norms (Darke et al, 2007:52). More challenging for users of these drugs is the imbalance caused by long term nervous system depression, and the difficult emotional and physical states involved in re- righting this. Pathophysiology of Dependent Opioid and Benzodiazepine Withdrawal As discussed, dependence on opioids or benzodiazepines brings with it tolerance, increased dosages, and then withdrawal symptoms with dose reduction. Symptoms include nausea, vomiting, insomnia, diarrhoea, shaking, sweating, extreme fear and anxiety, tremors, muscle spasm and pain, panic attacks, palpitations and hallucinations (Petursson, 1994; Erowid, 2010). A huge part of the difficulty for chronic users of these drugs is the sickness they experience physically, and the disturbed negative emotional state they experience mentally, when trying to withdraw from use. A further complication with benzodiazepines especially is that the symptoms elicited in withdrawal can often mirror those for which the drugs were prescribed initially, i.e. extreme anxiety, fear and muscle spasm. This can lead to withdrawal symptoms not being recognised as such, and further benzodiazepines being prescribed. Physiologically tolerance occurs as the dopaminergic system becomes impaired: a homeostatic response to repeated activation of the system. Through chronic use, baseline levels of dopamine function are reduced and usual rewarding phenomena no longer elicit the expected increase in dopamine transmission (Nestler, 2005:1446). This plays a role in the negative emotional symptoms associated with withdrawal. Chronic drug use is also related to changes in central corticotrophin releasing factors (CRF). CRF is part of the pathway involved in the stress response and release of cortisol. Abrupt withdrawal from opioids or benzodiazepines activates CRF neurones in the amygdala, bringing about fearful and aversive states (Nestler, 2005:1446). Study into the effects of withdra wal from opioids showed elevated

5 corticosterone and enhanced fear, illustrated by potentiation of the startle effect (Hamilton et al, 2013:73-4). To re-conceptualise this process then in energetic terms, withdrawal paints an interesting picture. With chronic use of central nervous system depressants, and overactive dopaminergic channels, the body is routinely being prevented from performing its usual functions, and cannot achieve homeostasis. Physiologically, this is equate to sedation, suppressed respiration, constipation, and reduced production of urine. There is stasis in the autonomic nervous system. In the language of tissue states, this equates to a cold, depressed state where tissues are under stimulated or incapable of responding to stimulation (Wood, 2004:50). In many cases, chronic under stimulation of tissues leads to a dry, withered, atrophic state. Often long term drug users appear emaciated. When the tissues are chronically undernourished, and underfed, they can dry and harden. A common symptom of atrophy is nervous exhaustion (Wood, 2004:489), exacerbating this cycle of drug seeking to calm nerves and difficult emotions. In withdrawal then, we can see the autonomic nervous system swing, pendulum like, to the other extreme in its attempt to achieve homeostasis. Its symptoms tend to be the opposite of those produced by intoxication of the drug itself (Rasmussen P, 1997:3). Tissues become over-excited and hyperresponsive. There is an exaggeration of the normalfunction-rate of the tissues (Thurston, 1900 cited in Wood, 2004:47). This manifests with symptoms like nausea, vomiting, diarrhoea, shaking and sweating, muscle spasms and the extreme fear and anxiety brought about by sympathetic overactivity in the fight or flight mode. Conventional approach to detoxification Conventional approaches to detoxification from each of these drug classes differ. Currently, there are no promising pharmacotherapeutic strategies for withdrawal from benzodiazepines. The most effective treatment is gradual dose reduction (GDR), with recommendation of seeking psychological help (Parr et al, 2009). The dose must be reduced gradually or more severe withdrawal symptoms are felt. This approach is in stark contrast to the mainstay treatment for withdrawal from heroin, which is methadone/buprenorphine maintenance (MMT) (Darke et al, 2007:50). Methadone is a full opioid receptor agonist and a weak NMDA receptor antagonist (Kreek et al, 2012:3390), acting on the same receptors as morphine and heroin, and eliciting many of the same effects. It is analogous to a medicalised heroin, but with a long half life, so only one dose per day is needed to suppress withdrawal symptoms (Rasmussen P, 1997:14). Methadone was introduced as a treatment for heroin users in the 1990s following HIV scares and

6 community responses to high crime rates in the economic downturn (O Brien, 2007). Its effectiveness however, is highly contested amongst policymakers, communities, drug users and frontline activists involved in addiction and recovery. Methadone is itself addictive, and carries with it many of the same adverse physical effects that heroin and other opioids bring: constipation, headache, difficulty urinating and insomnia. Withdrawal from methadone is similar to other opioids (O Brien, 2012). To exacerbate this, many methadone users continue other poly- drug use alongside it. In a study undertaken of 191 patients using methadone maintenance treatment, over half reported continual heroin use alongside (Senbajo et al, 2009:608). In 2012, Scottish drug and alcohol related deaths reached a record level, with methadone related deaths responsible for 47% of fatalities (bbc.co.uk, 2012). Despite the availability of methadone, heroin demand and use remains, and other treatment options such as rehabilitation are very limited. O Brien states, more and more people are becoming trapped in the cycle of methadone treatment because of the insufficient number of rehabilitation pathways (2007:43). A Holistic, Herbal Approach to Opioid & Benzodiazepine withdrawal A truly holistic approach to treating a patient in withdrawal, and more fully in recovery from addiction, would take into consideration their physical symptoms, emotional wellbeing, social circumstances, personal trauma and psychological state, and their support in the community to make choices and live according to their wishes and dreams. Obviously, herbalism is not the answer to all of these aspects of recovery, and a holistic herbal approach must work in concert with other professionals, family members and the person themselves. Importantly, a herbal treatment for withdrawal from these drugs must begin with the consent and will of the individual using the drugs. Addiction is a choice (Schaler, 1991:49), and attempts at hierarchical interventions that circumnavigate the choice and autonomy of that person are unlikely to succeed, and can jeopardise the trust of that person. If a drug user consciously and willingly chooses to detox, then herbs can play a big role in that process. O Brien adds to this that the support of others is key, as is the ability to reflect on the underlying causes of their addiction to find new and natural ways to manage life s challenges (2012). Taking all these points into consideration, an aspirational holistic model of addiction recovery is the Native American Wellbriety movement. Wellbriety takes the concept of sobriety further than pure abstinence, to a journey of healing and balance - mentally, physically, emotionally and spiritually (Coyhis & Simonelli, 2008:1927). Wellbriety does not ignore the social, political or economic roots of addiction, but acknowledges these causes without removing individual agency or the hard work required to heal. It is based on four laws of change:

7 1. a) Change is from within: it must come from the intent and choice of the person themselves 2. b) In order for development to occur it must be preceded by a vision: Change is not an accident. A person must develop a vision and move towards it. 3. c) A great learning must take place: Everyone must be part of the change; community recovery is needed to address the underlying social issues that give rise to anger, guilt, shame and fear that create the unhealthy soil in the forest 4. d) You must create a healing forest: The community must heal as the individual does. The individual affects the community and the community affects the individual (Coyhis & Simonelli, 2008:1927). Situating herbal support within a greater aspirational, community-driven movement such as the Wellbriety movement would be an excellent holistic approach to recovery. Herbs for Withdrawal and Detoxification Looking specifically at a herbal strategy for withdrawal, the most appropriate class of herbs to correct an over-excited tissue state and sympathetic nervous over-activity are relaxants. This approach mimics a gentler, non-addictive version of the drugs the patient is dependent on. This allows the pendulum to begin to swing back the other way towards homeostasis. Appropriate classes of herbs then include non-addictive nervines, sedatives, muscle relaxants and nervous trophorestoratives (O Brien, 2012). Specific herbs of use include Valeriana officinalis, Passilfora incarnata, Eschscholzia californica, Withania somnifera, Scutellaria lateriflora, Corydalis yanhusuo, and Viburnum opulus (Rasmussen P 1997, 2000; O Brien, 2012). A number of useful nervine herbs are also agonists to the benzodiazepine-gaba receptor complex, and can actually reduce the effects of withdrawal. These include Passiflora incarnate, Piper methysticum, Salvia militorrhiza, Scutellaria baicalensis, Matricaria recutita, Salvia officinalis and Withania somnifera (Rasmussen P, 1997:6). Adaptogens and antidepressants are also indicated, such as Bacopa monniera, Centella asiatica, Hypericum perforatum and Melissa officinalis (ibid). Each individual case must be looked at in its own particular context, to assess what kind of support is most appropriate for that person. Factors such as depression, hepatitis, insomnia, anxiety, cardiovascular health and any other medications or drugs they are taking will play a role in determining the individual prescription. Four particularly useful herbs for withdrawal are outlined in greater detail below: Passiflora incarnata

8 Passionflower has a long history of use as a sedative, anxiolytic herb with some analgesic properties (Rasmussen P, 1997:8). David Winston labels it as the most sedative of all the nervine herbs (2007:215). A double-blind, randomised controlled trial investigated the efficacy of Passiflora in the management of anxiety during withdrawal from opioids and found it to outperform Clonidine (Akhondzadeh et al, 2001). Valeriana officinalis Valerian has a wide range of uses, including anxiety, nervous disorders, insomnia and the physical symptoms of tension such as muscle cramping (Hoffman, 2003:592). Several studies suggest that Valerian is at least as effective as small doses of benzodiazepines as an anxiolytic sedative, without buildup of tolerance (Rasmussen P, 1997:7). Scutellaria lateriflora Skullcap is a superlative herb for cases where stress or anxiety cause nervous muscle spasm, tension or painful muscles (Winston & Maimes, 2007:217). Hoffman describes it as soothing nervous tension while actually rebuilding and renewing the nerves themselves. It is also useful in depression (Hoffman, 2003:583). Withania somnifera Ashwaganda is an Ayurvedic rasayana, or adapotgenic tonic herb, known also as a nervine restorative for general debility. It is commonly used clinically in benzodiazepine withdrawal, possibly acting as an agonist of GABA receptors (Rasmussen, 1997:8). As a calming adaptogen and nervine, it is very appropriate in cases of the nervous overactivity and anxiety associated with withdrawal. (Winston & Maimes, 2007:140). On a more physiological level, herbs such as Pimpinella anisum which reduce sugar based cravings by naturally raising blood sugar are also valuable (O Brien, 2012). Herbalist Rasmussen recommends using large doses of herbs in the initial phases of withdrawal due to the downregulation of receptors in the body built up through chronic drug use (1997:3). Another simple, but easily overlooked measure during detoxification and withdrawal is to avoid unnecessary stimulants like caffeine. Insomnia is a common symptom felt during withdrawal and supporting patients with sleep mixes can help give their bodies much needed rest and time for essential metabolic processes. Other herbal actions that will be of use later in the process are cleansing herbs, and individual organ support to detox the system particularly in the liver, bowels and kidneys

9 (O Brien, 2012). Useful liver herbs include Silybum marianum, Arctium lappa and Peumus boldo. Care should be taken with Arctium lappa and Peumus boldo as these are deep cleansers which could exacerbate the healing crisis brought about during the withdrawal and detoxification process. Their use is best left until the initial detoxification has subsided (Postlethwaite, 1997:49). Additional Therapeutic Approaches For an individual to move fully towards recovery, herbal medicine must sit in the wider picture of treatments and support from professionals and the community. There isn t room here to articulate the full scope of other practices and approaches, but it is essential to work with each person to make the right choices for them. A commonly used psychological model called Motivational Interviewing is commonly used in practice for this. MI avoids pressuring people to become drug free but instead encourages client empathy and works with the tensions between a person s current situation and how they would like their lives to be (Egan, 2010:191). This is achieved through one to one sessions with a counsellor or drug support worker who leads discussion with the person about their life and choices. For many people the process of detoxification is only one small step of the journey along the continuum of recovery, and being drug free might not take that person out of the cycles of abuse, poor self esteem and lacking opportunities they face outside of the clinic. We could learn a lot from the Native American Wellbriety movement s determination to heal the values of the community and create a nurturing, healing forest, as well as simply fixing the addict. References Adrian, Manuella & Hyg, M.S (2003) How can Sociological Theory Help Our Understandings of Addictions? in Substance Use & Misuse, Vol.38, No.10, pp Akhondzadeh, S et al (2001) Passionflower in the treatment of opiates withdrawal: a double -blind randomised controlled trial in Journal of Clinical Pharmacy and Therapeutics, Vol.26, pp Aldred, Elaine (2009) Pharmacology: A Handbook for Complementary Healthcare Professionals, Churchill Livingstone: China BBC (2012) Scots drug and drink-linked deaths at record level [online] available at: [accessed 12th December 2013]

10 Coyhis, Don & Simonelli, Richard (2008) The Native American Healing Experience in Substance Use and Misuse, Vol.43, pp Darke, Shane; Ross, Joanne; & Teesson, Maree (2007) The Australian Treatment Outcome Study (ATOS): what have we learnt about treatment for heroin dependence? in Drug and Alcohol Review, Vol.26, pp Davies A G et al (1999) Estimation of injecting drug users in the City of Edinburgh, Scotland, and number infected with human immunodeficiency virus in International Journal of Epidemiology, Vol.28, pp de Wet, C et al (2004) Benzodiazepine co-dependence exacerbates the opiate withdrawal syndrome in Drug Alcohol Dependence, Vol.76, No.1, pp.31-5 Egan, James (2010) Wider prevention: Poverty & Social Exclusion in Barlow, Joy (ed.) Substance Misuse: The Implications of Research, Policy and Practice, London: Jessica Kingsley Publishers, pp Erowid (2010) Heroin: Basics [online] available at: [accessed 9th September 2013] Hamilton, Kathryn L; Harris, Andrew; Gewirtz, Jonathan (2013) Affective and neuroendocrine effects of withdrawal from chronic, long-acting opiate administration in Brain Research, Vol.1538, pp Hoffman, David (2003) Medical Herbalism: The Science and Practice of Herbal Medicine, Vermont: Healing Arts Press Ilic, Goran;Karadzic, Radovan; Kostic- Banovic,Lidija & Stojanovic,Jovan (2005) Chronic IntravenousHeroin Abuse: Impact on the Liver in Facta Universitatis, Medicine and Biology, Vol.12, No.3, pp Jones, JD; Mogali, S; Corner, SD (2012) Polydrug abuse: a review of opioid and benzodiazepine combination use in Drug and Alcohol Dependence, Vol.1, No.125, pp.8-18 Kouros, Divsalar et al (2010) Opium and Heroin Alter Biochemical Parameters of Human s Serum in American Journal of Drug and Alcohol Abuse, Vol.36, pp

11 Kreek, Mary Jeanne et al (2012) Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics in The Journal of Clinical Investigation, Vol.122, No.10, pp Leshner, Alan I. (1997) Addiction is a Brain Disease, and It Matters in Science, Vol.278, No.45, pp Medicines and Healthcare Products Regulatory Agency (MHRA) (2011) Addiction to benzodiazepines and codeine: supporting safer use [online] available at: /CON [accessed 11th December 2013] Nestler, Eric J (2005) Is there a common molecular pathway for addiction? in Nature Neuroscience, Vol.8, No.11, pp O Brien (2007) Is there a way out of this clinic? An adult and community education perspective on Methadone and the Absence of Rehabilitation in The Irish Journal of Adult and Community Education, pp O Brien, Tom (2012) A natural approach to methadone detoxification focusing on the use of herbs [online] available at: ation-focus/ [accessed 3rd December 2013] Page C, Michael C, Sutter M, Walker M, Hoffman BB (2002) Integrated Pharmacology, 2nd Edition, C.V Mosby Publishing, USA Parr J, Kavanagh D, Cahill L, Mitchell G, Young R (2009) Effectiveness of current treatment approaches for benzodiazepine discontinuation: a metaanalysis in Addiction, Vol.104, Issue 1, pp.13 Patient (2013) Benzodiazepines and Z Drugs [online] available at: [accessed 12th December 2013] Petursson, H (1994) The benzodiazepine withdrawal syndrome Addiction, Vol.89, No.11, pp Postlethwaite, James (1998) Treating Addictions with Herbs, The European Journal of Herbal Medicine, Vol.No.2, pp Rasmussen, Phil (1997) A role for Phytotherapy in the Treatment of

12 Benzodiazepine and Opiate Drug Withdrawal in Modern Phytotherapist, Vol.3, No.3, pp.1-10 Rasmussen, Phil (2000) A role for Phytotherapy in the Treatment of Benzodiazepine and Opiate Drug Withdrawal. Part 2: Treatment Approaches to Opiate Withdrawal, and Conclusions in European Journal of Herbal Medicine, Vol.3, Issue 2, pp Rasmussen, Sandra (2000) Addiction Treatment: Theory & Practice, Thousand Oaks: Sage Publications Senbanjo, Richard et al (2009) Persistance of heroin use despite methadone treatment: Poor coping selfefficacy predicts continued heroin use in Drug and Alcohol Review, Vol.28, pp Winston, David & Maimes, Steven (2007) Adaptogens: Herbs for Strength, Stamina and Stress Relief, Vermont: Healing Arts Press Wood, Matthew (2004) The Practice of Traditional Western Herbalism, Berkeley: North Atlantic Books

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