Hyla Cass, MDLos Angeles CAwww.cassmd.com

CBD and the ECS

Addiction

Standard of care

Why medicate– or not?

Weaning off meds with CBD

Scientific ID - anandamide- in 1992 by Dr. Raphael Mechoulam

Began search in 1964 when as a post doc student, he discovered THC but – where did it fit in the body?

NIDA Discovery Award in 2011

See film “The Scientist” for his story

Involved in establishing and maintaining homeostasis throughout the body/brain

Facilitates communication between different cell types.

Connections and influence on immune, neurological, gastrointestinal, and endocrine systems

In the case of an injury or pain, system stabilizes nerve cells, calms immune cells, coordinates healing.

Modulation and balance are key aspects

Components: agonists, antagonists, receptors, enzymes, transports

Anandamide (N-arachidonoylethanolamine or AEA)A fatty acid neurotransmitter from the metabolism of eicosatetraenoic acid (arachidonic acid) an essential ω-6 polyunsaturated fatty acid The name is taken from the Sanskrit word ananda, which means "joy, bliss, delight” Partial agonist CB1 and CB2; metabolized by FAAHAnandamide 2-AG (2-arachidonylglycerol) is dominantFull agonist CB1 and CB2; metabolized by FAAH and MAGL

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Devane, W et al, "Isolation and structure of a brain constituent that binds to the cannabinoid receptor". 1992 Science. 258 (5090)Roger A. Nicoll and Bradley E. Alger, “The Brain’s Own Marijuana,” Scientific Ameri- can, December 2004 Mechoulam, R et al, Beyond THC and Endocannabinoids, Annual Review of Pharmacology 60(1), January 2020,

Mechoulam R, Fride E (1995). "The unpaved road to the endogenous brain cannabinoid ligands, the anandamides". In Pertwee RG (ed.). Cannabinoid receptors. Boston: Academic Press. pp. 233–258.

CB1 is the main receptor for THC, a phytocannabinoid(phyto meaning, “of the plant”); and, its endo-cannabinoid twin, anandamide, one of the body’s naturally occurring cannabinoids

The activation of CB1 receptors by THC is responsible for cannabis’ psychoactive effects.

Russo, Ethan B,(2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 163(7): 1344–1364.

Monocytes

Macrophages

B-Cells

T-Cells

Liver

Spleen

Tonsils

CNS

Enteric nervous system

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Atwood BK, Mackie K. CB2: a cannabinoid receptor with an identity crisis. Br J Pharmacol. 2010 Jun;160(3):467-79.

In immune system and periphery:

Cannabinoid pharmacology has been scientifically demonstrated

Phytocannabinoids: CBN, CBG, CBC, CBD, etc.

Terpenes: limonene, alpha-pinene, linalool, beta-caryophyllenereported to be important in the hemp entourage

Synergistic effect of phytocannabinoids and terpenes are greater than a single ingredient “magic bullet”

Russo, Ethan B,(2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid

entourage effects. Br J Pharmacol. 163(7): 1344–1364.

Natural component of cannabis. One of 85 or more active cannabinoids

Does not provide a “high,” not intoxicating

Counterbalance to THC; e.g. useful for countering THC side effects e.g.agitation, paranoia due to strains THC >> CBD

Half life 24 to 36 hours.

Sourced from hemp plant. Legal in most states, under 0.3% THC

• Dopamine

• Serotonin

• GABA

• Anandamide, 2 AG: inhibits FAAH

Kreitzer, A, Neurotransmission: Emerging Roles of Endocannabinoids, DISPATCH| VOLUME 15,

ISSUE 14, P.549-R551, JULY 26, 2005, https://doi.org/10.1016/j.cub.2005.07.005

The body synthesizes endocannabinoids that act as a “slow down” mechanism when neurons are stimulated by excitatory neurotransmitters (norepinephrine, glutamate)

Cannabinoid receptors also transmit chemical signals that inhibit the release of sedative NTs such as GABA which binds to the same receptor as Valium and alcohol, speeding things up.

Kreitzer, A, Neurotransmission: Emerging Roles of Endocannabinoids, DISPATCH| VOLUME 15, ISSUE 14, P.549-R551, JULY 26, 2005, https://doi.org/10.1016/j.cub.2005.07.005

• Does not induce adverse changes on food intake

• Does not induce catalepsy

• Does not affect physiological parameters (heart rate, blood pressure and body temperature)

• Does not adversely affect gastrointestinal transit, psychomotor or psychological functions.

• Chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans

Bergamaschi,Mateus, et al., (2011). Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent. Current Drug Safety., 2011, 6, 000-000

“Studies that evaluate whether CBD-drug interactions occur in clinical trials have to be performed.”

Metabolized by P-450 liver enzymes, so check the common enzymes – can inhibit drug metabolism eg blood thinners

Or can speed up drug metabolism cf grapefruit

Generally doses under 100 mg will not interfere with drug action

Though it’s most often well-tolerated, CBD can cause side effects, such as dry mouth, diarrhea, reduced appetite, drowsiness and fatigue.

Iffland, K . An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/

• Mental illness? • Moral issue? Will power?• Genetic?• Psychosocial aspects? • Biochemical?

Addiction Basics

• Rats fed junk food became addicted versus healthy diet • “Alcoholic” rats treated with amino acids lost their

cravings/addiction; • Lost the impulsivity often seen with alcohol withdrawal. • 1-week administration of CBD oil produced these effects

for 5 months, even though CBD itself left their systems after 3 days

• Williams, R. J., “A Nutritional Approach to Alcoholism,” in First Intl. Conference on the Alcoholic Beverages Research,June 2-4, 1958, C. Radouco-Thomas, ed., Pool Finsec S.A., Lausanne, Switzerland, 1959, 29-34.

• Repeated by Ken Blum as reported in The Healing Nutrients Within, Basic Health Pub, 2012, E. Braverman, C.Pfeiffer, K. Blum

• (3)Neuropsychopharmacology volume 43, pages2036–2045(2018

Is it psychological?

Inborn deficiency (in dopamine/motivator receptors) -> “Reward Deficiency Syndrome (RDS)”(Kenneth Blum)• “Self –medicate” in the form of drugs, alcohol, or thrill-

seeking, dangerous behavior to feel energized, motivated or happy.

• Predisposition only: you are not a slave to your genes!

Are We Programmed for Addiction?

• Kenneth Blum, PhD, Eric R. Braverman, MD. , Reward Deficiency Syndrome: A Biogenetic Model for the Diagnosis and Treatment of Impulsive, Addictive and Compulsive Behaviors.” Journal of Psychoactive Drugs; Vol. 32, Supplement; November 2000;

• Blum, Kenneth, Gondré-Lewis, Marjorie C., et al, Introducing Precision Addiction Management of Reward Deficiency Syndrome, the Construct That Underpins All Addictive Behaviors. Frontiers of Psychiatry, 2018; 9:548. Published online 2018 Nov 27

I can’t help it - it’s in my genes!

Epigenetics

Genetic Addiction Risk Score (GARS).

Gene Allele Prime FunctionDopamine D1 Receptor 48G Regulation of Dopamine Release in Accumbens

Dopamine D2 Receptor (ANKKI/DRD2 )

Taq I A1 Controls Synthesis of Dopamine D2 Receptors

Dopamine D3 Receptor (DRD3)

C Carriers sensitive to cocaine; opioids, alcohol and nicotine

Dopamine D4 Receptor (DRD4)

7R Pre-disposed to Novelty Seeking and ADHD

Dopamine Transporter (DAT1)

9R Fast transport of synaptic Dopamine back into pre-neuron leading to Hypodopaminergic trait.

Serotonin Transporter (HTTLPR )

S Fast transport of serotonin back into neuron

Mu-opiate Receptor (OPRM1)

G Predisposes to heroin addiction and pain sensitivity

GABA –B3 Receptor (GABAR3) 181. Predisposes to anxiety disorders

Mono-Amine –Oxidase A (MAO-uVNTR)

3R Fast catabolism of mitochondria Dopamine

Catecholamine –Methyl-Transferase (COMT-vall58met)

G Val substitution leads to fast catabolism of synaptic Dopamine leading to RDS

Blum, K. et al. Genetic Addiction Risk Score (GARS): Molecular Neurogenetic Evidence for

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• Early childhood trauma- ACEs study, Felitti, 1998• Peer pressure• Stress• Environment – rat park experiment

Psychosocial Factors

• Felitti V et al. Relationship of Childhood Abuse and Household Dysfunction to Many of the Leading Causes of Death in Adults. May 1998 Volume 14, Issue 4, Pages 245–258 https://doi.org/10.1016/S0749-3797(98)00017-8

• https://www.cdc.gov/violenceprevention/acestudy/index.html• Alexander, B.K., Coambs, R.B., and Hadaway, P.F. (1978). "The effect of housing and gender on morphine self-

administration in rats," Psychopharmacology, Vol 58, 175–179. PMID 98787• https://www.psychologytoday.com/us/blog/all-about-addiction/201508/addiction-connection-and-the-rat-park-

study

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• Nutrient and neurotransmitter deficiencies

• Specific laboratory testing

• Provide needed macronutrients, vitamins, minerals, and amino acids.

Biochemical Factors

Neurotransmitters (urine, red blood cell)Hormones :

Thyroid (free T3/T4,TSH)CortisolDHEA-SEstradiolProgesteroneTestosterone-total & freeHeavy metals- hair, provoked urine, serum

CBCChem panel w fasting glucose

If indicated: Hbg A1C (glycohemoglobin)Amino acids (plasma,urine) Vitamins and mineralsEssential fatty acidsOrganic acids

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Laboratory Testing

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Clinical observation:

• Often sufficient to stop the cravings for carbs cocaine,

heroin, benzodiazepines, sugar, caffeine; habits like

gambling, shopaholic

• Substitution of sugar, caffeine, nicotine, etc for drug of

choice perpetuates the addictive cycle

lum K, et al, The D2 dopamine receptor gene as a determinant of reward deficiency syndrome.J R Soc Med. 1996 Jul; 89(7):396-400

Blum K et al, Dopamine and glucose, obesity, and reward deficiency syndrome, Front Psychol.2014;919. Published online

2014 Sep 17. doi: 10.3389/fpsyg.2014.00919

Diet and Supplements

·

Raw materials from diet: • Carbohydrates, fats, protein (amino acids)• Vitamins, minerals, flavonoids:

Co-factors to catalyze the chemical processes; antioxidants, neuroprotective

• Make neurotransmitters = brain messengers• Imbalance leads to cravings, addiction, withdrawal

Basic Requirements

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• GABA: dampens, calms, balances

• Dopamine, Adrenaline & Noradrenalin:

energizing, focus, stress response, “feel-good”

• Serotonin: mood, calm, appetite control

• Endorphins: euphoria, pain control

• Acetylcholine: memory and alertness

• Down regulation stops the fun: we need more andmore of the stimulant substance to feel good andto maintain our energy level

• Vicious cycle of stimulant dependence and fatigue• Fatigue (leading to stimulant cravings) can have

many sources, including poor sleep and diet,chronic infection, and hormone imbalances.

• Similar cycle with downer addiction (benzos)

Dynamics of Addiction

Treat underlying genetic/acquired NT imbalances and deficiencies

Treat underlying psychiatric conditions

Cravings are caused by deficiencies in one of more NT systems

End addictions by restoring balance

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Blum, K et al. Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors. J Psychoactive Drugs. 2000 Nov;32 Suppl:i-iv, 1-112.http://www.ncbi.nlm.nih.gov/pubmed/11280926

Endocannabinoids, stress hormones, and dynorphin are potential substrates for the rewarding effects of abused substances.

Cannabinoids and endocannabinoids appear to be involved in adding to the rewarding effects of addictive substances, including, nicotine, opiates, alcohol, cocaine, and BDZs.

Onaivi, Emmanuel S, (2008) An Endocannabinoid Hypothesis of Drug Reward and Drug Addiction Ann. N.Y. Acad. Sci. 1139: 412–421 (2008). C 2008 New York Academy of Sciences. doi: 10.1196/annals.1432.056

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The results suggest that the ECS may be an important natural regulatory mechanism for drug reward and a target for the treatment of addictive disorders.

Activation of DA pathways – directly/indirectly involved in brain-stimulation reward of all brain sites related to addiction

All NT systems are interconnected and involved in the reward cascade

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Onaivi 2008

Role of CBD in Addiction

Conclusion: CBD supports the endocannabinoid system (ECS) which is found to be low in individuals who are addicted to opiates and other substances of abuse, as well as to psychiatric medications. The administration of the phytocannabinoids found in full spectrum CBD helps raise the ECS, allowing an easier and faster transition, as well as providing therapeutic benefits for underlying conditions such as pain, depression and anxiety.

Onaivi, Emmanuel S, (2008) An Endocannabinoid Hypothesis of Drug Reward and Drug Addiction Ann. N.Y. Acad. Sci. 1139: 412–421 (2008). C 2008 New York Academy of Sciences. doi: 10.1196/annals.1432.056

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• Huge burden of addiction: drugs, behaviors, foods• Endocannabinoid deficiency is common • CBD addresses pathways of addiction • CBD is supported in preclinical studies & practice • Minimal adverse effects, toxicity or drug interactions • Dosing is modest with fast results

Inhibits sensitization

Blocking reconsolidation in amygdala (PTSD)

Inhibits drug seeking (heroin)

Cuts cravings for opiates (need THC?)

Prevents cell death/brain volume loss (AD, TBI)

Sustained effects after treatment (nicotine)

Inhibiting anxiety, epilepsy, brain injury (alcohol, crack)

Blessing, E, Cannabidiol as a Potential Treatment for Anxiety Disorders.Neurotherapeutics. 2015 Oct; 12(4)Fischer B, et al, Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use., Int J Drug Policy. 2015 Dec;26(12):1177-82. Morgan et al. Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings,Addict Behav. 2013 Sep;38(9):2433-6. Ren y., Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances, Journal of Neuroscience 25 November 2009, 29 (47) 14764-14769

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Cannabidiol (CBD), the second most abundant component of cannabis, is thought to modulate various neuronal circuits involved in drug addiction.

14 studies, 9 on animals; 5 on humans.

A limited number of preclinical studies suggest that CBD may have therapeutic properties on opioid, cocaine, and psychostimulant addiction,

May be beneficial in cannabis and tobacco addiction in humans. Further studies are clearly necessary to fully evaluate the potential of CBD as an intervention for addictive disorders.

Prudhommme, M, Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence, Substance Abuse: Research and Treatment 2015:9 33–38

More than 64,000 Americans died from drug overdoses in 2016, including illicit drugs and prescription opioids, according to the CDC. That’s nearly double the number of fatal overdoses a decade ago.“Medical and adult-use cannabis (availability) were associated with lower opioid prescribing rates: Marijuana is one of the potential, non-opioid alternatives that can relieve pain at a relatively lower risk of addiction and virtually no risk of overdose”Type 1 cannabinoid receptors (CB1R) are co-localized with opioid μ opioid receptors (which mediate the actions of opioid drugs) in neurons of the nucleus accumbens and dorsal striatum that modulate reward, goal-directed behavior, and habit formation relevant to addiction

Rodriguez JJ, et al. Ultrastructural localization of the CB1 cannabinoid receptor in mu- opioid receptor patches of the rat Caudate putamen nucleus. J Neurosci. 2001;21:823–833.[Wen, H. Association of Medical and Adult-Use Marijuana Laws With Opioid Prescribing for Medicaid Enrollees. JAMA Internal Medicine, 2018

After acute withdrawal is over 4-14 days dep on short or long-acting, PAWS may begin – weeks, mo’s, even years: anxiety, depression, pain, insomnia, etc

Daily CBD is excellent for treating this

Increase NTs including serotonin, alleviate depression, anxiety, pain, and even eliminate cravings and drug-seeking behavior.

Case examples using CBD; shortens withdrawal

Hurd, Y et al, Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage. Neurotherapeutics. 2015 Oct; 12(4 Published online 2015 Aug 13;

Wen , H. Association of Medical and Adult-Use Marijuana Laws With Opioid Prescribing for Medicaid Enrollees. JAMA Internal Medicine, 2018;

Wiley. "Marijuana legalization reduces opioid deaths." ScienceDaily. ScienceDaily, 7 August 2019. <www.sciencedaily.com/releases/2019/08/190807092350.htm>.

Repeated CBD use will induce plastic changes in the brain.

Clinical studies have supported the beneficial effects of CBD in anxiety, depression, PTSD, schizophrenia, seizure disorders, multiple sclerosis, and more

Neuroprotective, antioxidant, anti-inflammatory

Non-addictive

Campos, Alline, et al., (2017). Plastic and Neuroprotective Mechanisms involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders. Frontiers in Pharmacology. Volume 8, Article 269.Bergamaschi et al., 2011a; Lewke et al., 2012, Liggresti et al., 2016

Physicians are taught how to put people on psych meds, but not how to safely and effectively wean them off.

Serious gap in competency

Better modelMore physiologically based, with various modalities & nutrients, including full spectrum cannabis with 0.3% or less THC -- >”CBD”

More patient-centered "reveal and rebalance” vs “command and control”

“You’re on it for life - like insulin”

Cold turkey –> discontinuation syndrome

Gradual but often not slow enough for the individual

No ancillary support to restore brain chemistry balance

Efficacy not always there- “medication resistant”

Relapse despite meds

“I want myself back”

Original stressful situation has resolved

Weight gain, metabolic syndrome, type 2 diabetes

Sexual side effects

TD, neuroleptic malignant syndrome

Suicidal, homicidal

Cass,H, Supplement Your Prescription, Basic Health Publications 2008Bahl S. Psychother Psychosom, 2003; Steingart A Int J Epi2003

• Meta-analysis of 6 PCDB studies (718 patients), minimum 6 wkson meds or placebo

• Most patients with severe symptoms had some drug benefit• All others (mild, moderate and some severe depression

patients) were same as placebo — but with side effects.CONCLUSION: The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.

Fournier et al, Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010;303(1):47-53

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“Continued drug treatment may induce processes that are opposite of what the medication originally produced.”

This may “cause a worsening of the illness, continue for a period of time after discontinuation of the medication, and may not be reversible.”

El-Mallakh, R. “Tardive dysphoria: The role of long-term antidepressant use in inducing chronic depression. Medical Hypotheses 76 (2011): 769-773. Breggin, Peter, Psychiatric drug-induced Chronic Brain Impairment (CBI): Implications for long- term treatment with psychiatric medication, International Journal of Risk & Safety in Medicine 23 (2011) [http://breggin.com/wp- content/uploads/2012/01/Breggin2011_ChronicBrainImpairment.pdf]

Healing power of Nature - best pharmacy

Identify and treat the root cause, not the symptoms: science/art of medicine

Safely and naturally as possible, non-invasive treatments that minimize the risks of harmful side effects when possible

Doctor as teacher-> partnership

Treat the whole person: complex interaction of physical, mental, emotional, genetic, dietary, environmental and lifestyle factors.

Meta-analysis: 13 studiesCognitive decline noted on meds: all 12 areas of psychological evaluation3 mos to 3 yrs after withdrawal: Significant cognitive decline noted in 5 areas: visual- spatial, attention and concentration, problem solving, general IQ, psychomotor speed. Several studies in adult populations have reported strong associations between benzodiazepines and all cause mortality, even for short durations of treatment

Stewart, S, The effects of benzodiazepines on cognition. J Clinical Psych 2005, 66: (2): 9-13 Patorno, E, Benzodiazepines and risk of all cause mortality in adults: cohort study, BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j2941 (Published 06 July 2017)

Risks of Benzos

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• Look for nutrient and neurotransmitter deficiencies• r/o issues in GI, HPA axis, toxicities, inflammation,

infection, blood sugar, hormones, • Specific laboratory testing• Provide needed vitamins, minerals, and amino acids• Utilize the endocannabinoid system to mitigate

withdrawal effects, to rebalance NT’s, and more

Biochemical factors to address pre-weaning

Can positively shift mood/NT’s with: Lifestyle changesMusic, massage, movement, etc*MeditationPsychotherapy – including PTSD (HPA axis)Neurofeedback

Overall, neurofeedback training appears to be an efficacious treatment modality that promotes high rates of abstinence for individuals with substance use disorders.

Shepard, James C. Neurofeedback Training for Substance Use Disorders: A Review of the Applicability in Treatment, article 68 (many refs listed) Vistas online 2015

Priddy, Sarah E et al. “Mindfulness meditation in the treatment of substance use disorders and preventing future relapse: neurocognitive mechanisms and clinical implications.” Substance abuse and rehabilitation vol. 9 103-114. 16 Nov. 2018, doi:10.2147/SAR.S145201 45

Psychiatric drugs perturb neurotransmitter systems, which cause changes in receptor densities.

During the withdrawal process, these receptor densities must renormalize, which may take an extended period of time.

Withdrawal symptoms vary by receptor type, and half-life of drug

Renoir, T., Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved, Front Pharmacol. 2013; 4: 45. Apr 16. doi: 10.3389/fphar.2013.00045

Neurotransmitter Receptors: Downregulation

Psychiatric drugs act on more than one receptor type.

There are feedback loops in the brain that cause perturbations in

one neurotransmitter system to cause changes in others

(such as feedback loop between dopaminergic & serotonergic activity)

In the same class of drugs, individual drugs may have different binding profiles and varying half-lives, which lead to varying withdrawal symptoms.

Patients often take several classes of psychiatric drugs, and there is no model that explains the physiology of brain changes caused by polypharmacy, or the possible renormalization of neurotransmitter systems following withdrawal from multiple drugs.

ibid

With gradual withdrawal, the receptors will return to normal densities more gradually, reducing the severity of withdrawal symptoms and risk of relapse.

Usual: Lower by 10% of the total daily dose every 14 days, until 50% is reached. Then lower by 10% of that dose for the remainder.

Some patients require smaller dose reductions, some longer time intervals.

If symptoms hard to tolerate, go back up to last dose.

Exact mechanism is unclearIbid.

2 withdrawal windows: acute 72 hours after a dose change where patients may experience physical symptoms like headache, fatigue, nausea, and even “brain zaps”

Most often resolves, with other occurring around 2 months after the dose change or final dose: PAWS

It’s not likely a relapse, but protracted withdrawal

Note times, events:

Dose of med, of supplement

Symptoms: list, rate severity 1-10

Sleep (amount, quality etc.)

Lifestyle: exercise, stressors

Note when there is a major improvement

50-86% experience:

Flu-like symptoms

Tingling or electric shock sensations “brain zaps”

GI problems

Disturbed sleep and insomnia

Fatigue

Dizziness

Depression and Anxiety

Less, but too often: suicidal, homicidal

The SSRI discontinuation syndrome. Haddad P1, J Psychopharmacol. 1998;12(3):305-13.

“Often, the brain becomes accustomed to these medications and they often lose their effectiveness, requiring higher doses or different drugs. In contrast to anxiolytic drugs, there are herbs and nutrients which can stimulates neurotransmitter synthesis and more naturally effect and even adjust brain chemistry in the absence of many of the side effects experienced with drugs. Therefore this paper explores several herbal and nutritional approaches to the treatment of anxiety.” (cont’d->)

Alramadhan, E, et al. Dietary and botanical anxiolytics. Med Sci Monit 2012; 18(4): RA40-48

Initial test: reduce by 10- 25% q14 days

Stable for at least 5 days and 14-days have passed since last reduction

Use compounding pharmacy if needed; titrate based on tolerance

Add: 5HTP (100-300 mg) or Tryptophan (1000-3000 mg) + co-factors

Take precursor 6 hours away from SSRI dose

SE precursor boosts effect of SSRIs which deplete SE

Alramadhan, E, et al. Dietary and botanical anxiolytics. Med Sci Monit 2012; 18(4): RA40-48

Slowly taper drug, increasing precursor as needed.

Add GABA , theanine as needed

Omega -3 for brain zaps- 3 gm + prn

CBD smooths the ride

Substitute fluoxetine for SNRI’s and shorter acting SSRIs?

SNRI: may need to add catecholamine precursor

Often need to go more slowly

Levitan, RD et al, Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.J Psychiatry Neurosci. 2000 Sep;25(4):337-46.

Questionable to switch to longer-acting diazepam (Ashton protocol) –may compound the issue –different pathways; it just adds one more prodrug/problem

Prolonged and difficult withdrawals on Ashton’s site: no quick answer ; individualized plan

She is against using nutrients but those of us who do, find them invaluable

Ashton, Professor C Heather, Benzodiazepines: How They Work and How to Withdraw, (The Ashton Manual)Revised 2002

Without nutrient support may take several months to years

Start with a 5% reduction, reduce again in 14 days and repeat at the 5% reduction two additional times. If successful, continue at 5%. Some can handle 10%: do with care.

If withdrawal side effects begin, go back to the last dosage doing well and for the next reduction, reduce at a more gradual rate, like 2%.

Preclinical evidence: “Strongly supports CBD as a treatment for GAD, panic, social anxiety disorder, OCD and PTSD…Human experimental findings support preclinical findings and also lack of anxiogenic effects, minimal sedative effects, and an excellent safety profile…Need more clinical studies and dosing information”.

Blessing, EM et al Neurotherapeutics 2015 September 4th (epub)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/

Titrate prn for symptom relief

Shortens withdrawal period

Potentiates the targeted aminos/NTs

Start low and slow eg ½ dropper or 12.5 mg (if 2 oz 1500 mg bottle), then 1 dropper etc

Can go up to 100 even 200 mg/d acutely

Titrate prn for symptom relief

Shortens withdrawal period

Potentiates the targeted aminos/NTs

Start low and slow eg ½ dropper or 12.5 mg (if 2 oz 1500 mg bottle), then 1 dropper etc

Can go up to 100 even 200 mg/d acutely

PTSD – traumatic events affecting current lifeAnalogy - old computer programStarted as first aid, becomes chronic, destructiveActivates HPA axis, which affect immune system, inflammation, sympathetic dominanceNeed to uncover and clear it/revise historical emotionsVarious techniques – EMDR, SE, EFT, etc

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People with PTSD and with chronic stress show elevated CB1R availability and reduced peripheral AEA, suggestive of reduced eCB toneCBD has been useful in “clearing traumatic memory” by mitigating the fear response

Bassir, Nia A1, et al. Endocannabinoid System Alterations in Posttraumatic Stress Disorder: A Review of Developmental and Accumulative Effects of Trauma. Chronic Stress (Thousand Oaks). 2019 Jan 1;3 https://www.ncbi.nlm.nih.gov/pubmed/31660473Qin Z, Zhou X, Pandey NR, et al. Chronic stress induces anxiety via an amygdalar intracellular cascade that impairs endocannabinoid signaling Neuron. 2015;85:1319–1331. Hill, M, et al., (2013). Reductions in Circulating Endocannabinoid Levels in individuals with Post-Traumatic Stress Disorder Following Exposure to the World Trade Center Attacks. Psychoneuroendocrinology. 38 (12).Neumeister A. The endocannabinoid system provides an avenue for evidence-based treatment development for PTSD. Depress Anxiety. 2013;30:93–96. doi: 10.1002/da.22031.

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CBD hold promise as an anti-psychotic vs neuroleptics which simply dampens intensity, with side effects, while CBD has side benefits

Used in treating movement disorders (HD, PD), it has also been found to neutralize TD in mouse model. CBD also prevented LPS-stimulated microglial activation, an effect that was also antagonized by GW9662 (a PPARγ antagonist). In conclusion, our results suggest that CBD could prevent haloperidol-induced orofacial dyskinesia by activating PPARγ receptors and attenuating neuroinflammatory changes in the striatum.

• Leweke FM et al, Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia Translational Psychiatry 2012 Mar; 2(3): e94.

• Peres et al. 2.Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders? Front Pharmacol2018; 9: 48 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958190/

• Cannabidiol prevents haloperidol-induced vacuos chewing movements and inflammatory changes in mice via PPARγ receptors. Sept 2018. https://www.ncbi.nlm.nih.gov/pubmed/30217539#.

Dec 2017, 87 yr old woman on 4 different psych meds x 2yrs, “bipolar.” About to be placed in dementia care facility. Had tried to wean off unsuccessfully in past. Most of the interview was done with her daughter, as patient was lethargic, and had seriously impaired memory

We began a gradual weaning program, supported by cognitive formula, Vit D 5000 IU, Omega 3’s and CBD tincture+ 25 mg CBD capsule, gradually adjusted dose as needed. Continued on 25 mg cap bid + other supps (sporadic on supps but consistent with CBD). (cont’d ->)

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“We (myself and my husband) would just like to thank you

for what you did for my mother. She has never been so

good!. Her reaction to the CBD was amazing. She did not

have any side effects. The opposite, she is very sharp,

energetic, and all her functions are perfect. She is

remembering things, is interacting. We have her back, and

even better!”

Update 2 years later

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Start low and titrate up: 8 mg-100 mg and more

Bioavailability of oral CBD in humans is around 6% (large first pass effect)

CBD vs Clonazepam: side effect profile

Cannabidiols, agreed upon safety in humans up to 1,500 mg

No great long term studies to date. Mostly acute dosing.

Broad spectrum, full spectrum, CBD isolate

Organic, Non GMO, with C of A (no pesticides, heavy metals, chemicals, mold, bacteria, etc)

CO2 extraction preferred but difficult in large production; or remove solvents

Label: mg of CBD per 1 or 2 oz bottle; see actual amount per dose

Tincture: various: include nano-emulsified= water based (better absorption)

Capsules: hard caps, gelcaps, some nano-emulsified

Topical – salves, creams • Sprays

Transdermal – patches. • Vape (eg acute pain, migraine)

“Full spectrum hemp oil extract”- look for mg of phytocannabinoid diols on label. Why? Legal limbo on Fed level

Cannabis has a long tradition in the healing arts – and a great future!

The ECS plays a central role in most biological systems

CBD is well tolerated and has a positive effect on the CNS

CBD is an outstanding tool for a range of psychiatric disorders- “new” model of

tx : effective, low/no side effects, less costly; treats anxiety (incl PTSD, OCD,

social anxiety), depression, psychosis, drug withdrawal, pain, addiction, etc

Supports body/brain chemistry vs just targeting the symptom/side effects

Replace or augment meds?

“First do no harm”

HYLA CASS, M.D.4712 Admiralty Way #165Marina del Rey CA 90292

www.cassmd.com

office@cassmd.comUse subject line: “IHS request/comment”

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