Terpenes

Pinene

Pinene is one of the most most commonly occurring terpene in nature. Evidence regarding pinene iis mostly limited to preclinical studies, well-designed clinical trials are lacking. Nevertheless, existing data suggests that pinene and linalool are relevant candidates for further investigation as novel medicines for illnesses, including stroke, ischemia, inflammatory and neuropathic pain (including migraine), cognitive impairment (relevant to Alzheimer’s disease and ageing), insomnia, anxiety, and depression. Several plants high in pinene have been used in traditional medicines for a variety of conditions, such as gastrointestinal disturbances, seizures, inflammation, pain, snake bite, colds and fevers, hypertension, rheumatism, cancer, fungal infection, anxiety, and depression amongst others.

 

 

 

Links to other Pertinent Educational Pages:

Links to ALL Marijuana Educational Pages

 

Terpenes:

Terpenes – An Overview

 

Terpenes Therapeutic Benefits

 

Individual Terpenes:

 

 

 

The medical information on this site is provided as a resource for information only, and is not to be used or relied upon for any diagnostic or treatment purposes and is not intended to create any patient-physician relationship.  Readers are advised to seek professional guidance regarding the diagnosis and treatment of their medical concerns.

 

 

Key to Links:

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Definitions and Terminology

 

 

Terpenes

More than 540 chemicals, including 18 different chemical classes, more than 100 different cannabinoids (including THC and CBD) and more than 400 terpenes have been identified in marijuana plants (cannabis). In addition, a group of compounds called flavonoids – about 20 of them – have also been identified in cannabis. Flavonoids, one of the largest nutrient families known, are a group of plant metabolites thought to provide health benefits through cell signalling pathways and antioxidant effects. It is believed that the therapeutic benefits attributed to cannabis are derived from all of these families of compounds. This page focuses on terpenes.

 

What are Terpenes (or Terpenoids)?

Terpenes are fragrant essential oils manufactured by many different types of plants and herbs, including cannabis. Terpenes contain only hydrocarbons while terpenoids are oxygen-containing terpenes. Terpenes (and terpenoids) are organic chemicals produced by most plants, as well as some animals such as swallowtail butterflies and termites. Terpenes are volatile aromatic molecules, meaning they evaporate easily, and are some of the primary components of plant resins and flowers, providing flavor and fragrance to fruits and spices commonly found in a normal diet. Terpenes, not cannabinoids, are responsible for the aroma of cannabis and are the source of the aromas, flavors, and other characteristics that help distinguish different cannabis strains.

See: Types of Terpenes and Terpenoids

 

Alpha-pinene (α-pinene)

In nature, two structural isomers of this terpene exist, α-pinene and β-pinene. One study reported average α-pinene and β-pinene concentrations of 15 and 21% across 17 hemp varieties.  Pinenes are found in cannabis strains like Jack Herer, Strawberry Cough, Blue Dream, Island Sweet Skunk, Dutch Treat and Romulan. They are also found in pine needles, conifers, and many herbs such as parsley, basil, and dill. These terpenes are also the major constituents of turpentine, and are abundant in rosemary and lavender. α-pinene is the main compound found in frankincense (Boswellia frereana), myrtle, juniper, camphor, and conifers.

 

Pinene’s low molecular weight and high lipophilicity suggests it likely penetrates the blood brain barrier and studies indicate that pinene can enter the brain following oral ingestion or inhalation.  α-pinene and β-pinene do not appear to have an appreciable binding affinity for CB1 or CB2 receptors. The mechanisms underlying α-pinene-induced pain benefits are unclear but may involve GABAA and μ-opioid receptors However, the ability of pinene to reduce pain in inflammatory states and exert longer-lasting analgesia suggests that pinene has a broader mechanism of action than only activity on the opioid receptors.

 

All of the studies below and the conclusions they have provided represent only pre-clinical lab and animal studies that have investigated pinene for its medicinal properties. They have provided suggestive benefits only, until clincal human studies are performed for conclusive evaluation. Although pinene is promoted as beneficial for pain and/or anxiety, there are no human studies to support this claim.

 

 

Alpha-pinene has been found to have sedative, hypnotic, and anxiolytic properties along with significant anti-inflammatory and analgesic benefits. Terpene strains that are high in α-pinene and terpinolene may provide an uplifting effect. Pinene also plays an insect-repellent role in plants and is a bronchodilator in humans at low exposure levels, suggesting benefit in asthma. It is an acetylcholinesterase inhibitor that may reduce short-term memory impairment from THC. Claims have been made that it improves a person’s ability to focus their attention as well as to reduce perception of stress.

Pinene acts on multiple neurologic pathways, including GABAergic, cholinergic, dopaminergic, serotoninergic, adrenergic, noradrenergic neurotransmitter systems. It acts in multiple regions of the brain including the hippocampus, frontal cortex, striatum and midbrain.

 

Therapeutic Benefits of Pinene

Anti-inflammatory and Analgesic Effects – Arthritis

Pinene is one of the dominant terpenes found in cannabis strains known to benefit chronic pain. Alpha-pinene’s anti-inflammatory and analgesic benefits take place through inhibition of COX-2, the same system in which NSAIDs like ibuprofen work. Pinene is also anti-inflammatory via prostaglandin PGE-1 and its antioxidant and anti-inflammatory effects in human chondrocytes (cartilage cells), suggests potential benefit in arthritis with analgesic benefits as well.

 

SARS-CoV

Essential oils have been evaluated for their inhibitory activity against SARS-CoV replication in the lab. L. nobilis oil, containing beta-ocimene, 1,8-cineole, alpha-pinene, and beta-pinene as the main constituents appears to have antiviral activity against SARS-CoV. Pinene also acts as a broad-spectrum antibiotic and has also been shown to have prominent activity against antibiotic-resistant staph bacteria (MRSA). These properties may contribute to the disinfectant properties of Pine-Sol,® a multi-surface cleaner.

 

Antioxidant

Studies have shown that α-pinene, β-caryophyllene and linalool up-regulate Nrf2 activity to protect cells from oxidative damage. Nrf2 (nuclear factor erythroid 2) is a transcription factor that is involved in cellular responses to oxidative damage and inflammation. See:Nrf2 Activators

 

Anxiety and Sleep

Pinene exerts its effects on the brain through its ability to act as a positive modulator of the major inhibitory neurotransmitter, γ-aminobutyric acid (GABA)A by binding to this benzodiazepine site to improve sleep. It significantly increases the duration of non-rapid eye movement sleep (NREMS), and reducing sleep latency (time to fall asleep).

 

β-Pinene

Related to α-pinene, β-Pinene is another important monoterpene present in different strains of Cannabis. β-pinene has antimicrobial, antiseptic and antioxidant activity. It also may have anti-depressant-like and sedative-like properties. The mechanisms for these benefits are unknown but theorized to be related to the serotonergic  adrenergic and/or dopaminergic systems. α-pinene and β-pinene inhibit the activity of acetylcholinesterase in the brain and are thought to aid memory and minimize cognitive dysfunction induced by THC intoxication.

 

Overall, existing pre-clinical studies still require replication in human trials to confirm the effectiveness and safety of pineness. Nevertheless, with initial research demonstrating their psycho-pharmacological and anti-inflammatory effects, pinene isomers may be of use treating anxiety and depression, while their combination of anti-inflammatory and analgesic properties suggest they may be suitable for treating chronic pain, especially arthritis, but further research is needed.

 

Pharmacology of Pinene

The mechanisms of action of pinene are still unclear but the low molecular weight and high lipophilicity of monoterpenes, including pinene, suggest that they can penetrate the blood brain barrier and therefore directly impact the brain. In fact, in animal studies α-pinene was detected in brain after 30 min of exposure via inhalation. Additionally, α- pinene levels were 2-fold higher when delivered as an oil blend (i.e., via inhalation in the presence of other essential oils: p-cymene, 1,8-cineole, and limonene), suggesting that uptake of α-pinene by the brain can be enhanced by the presence of other terpenes. Another study examined the pharmacokinetics of α-pinene isomers in humans during 2 hours of exposure by inhalation while performing low intensity exercise. It showed a 60% relative pulmonary uptake of α-pinene (i.e., concentration in inhaled vs. exhaled air), with blood levels that increased in a linear dose-dependent manner. Blood levels rapidly 6 hours after exposure.

 

Anxiety and Depression

α-pinene and β-pinene do not appear to bind with CB1 or CB2 cannabinoid receptors peripherally or in the brain. Pinene exerts its effects on the brain by direct binding to GABA-A-Benzodiazepine receptors (GABAA-BZD) and as a partial modulator at the GABAA receptor (the benzodiazepine site) to improve sleep. It potentiated the response of GABAA receptors to the the major inhibitory meurotransmitter GABA. In addition, β-pinene targets the serotonin 5-HT1A, and β-adrenergic receptors to exert antidepressant effects, suggesting that β-pinene may have similar properties to the anti-depressant drugs that target monoaminergic (eg serotonin and norepinephrine) signalling in the brain (SSRIs like Prozac and SNRIs like Cymbalta). Several animal studies have examined the effectiveness of α-pinene and β-pinene as well as essential oil blends rich in pinene in treating anxiety- and depressive-like behaviours, with a positive findings, but human studies are still lacking.

Oxidative Stress, Inflammation, and Nerve Damage

Lab studies show that pinene protects against oxidative stress, inflammation, and neuronal damage. α-pinene directly inhibits inflammatory signalling pathways in immune cells. For example, α-pinene reduces pro-inflammatory cytokines [interleukin-6 (IL-6), tumour necrosis factor-α (TNF- α), and nitric oxide (NO). Pinene has also been shown in lab studies to have neuroprotective properties in multiple models of  neurological illnesses including decreasing the size of strokes.  These studies are preliminary only.

 

Analgesia in Inflammatory and Neuropathic Pain

In animal studies α-pinene (5–25 mg/kg, orally) provided pain relief and reduced inflammation following topical application of irritants that lasted for 48 hours. Repeated pinene treatment prevented mechanical sensitization associated with sciatic nerve compression in a rodent model, with effectiveness similar to existing drugs used to treat neuropathic pain (indomethacin and gabapentin). Compared to morphine, one study reported lower peripheral pain response in mice following α-pinene treatment, with longer lasting effects.  The mechanisms underlying proposed α-pinene-induced analgesia are unclear but may involve GABAA and μ-opioid receptors based on the benefits being prevented by pre-treatment with GABAA and μ-opioid receptor blockers, Evidence is limited to single studies and more research is needed.

 

 

Insomnia

Essential oils rich in α-pinene and β-pinene have been used in traditional medicine to aid sleep for centuries. In sleep studies in mice, α-pinene increased sleep duration and reduced the time to fall asleep in a dose-dependent manner. α-pinene also potentiated GABAA receptor inhibition  which was blocked by flumazenil, a benzodiazepene antagonist. Pinene metabolites, myrtenol and verbenol, have also been shown to interact with GABAA receptors. Together, these results demonstrate that α-pinene can regulate GABAergic inhibitory tone by influencing GABAA signalling, and may improve sleep through interactions with the GABAA receptor benzodiazepine site.  Clinical trials examining the efficacy and safety of isolated pinene isomers on sleep are also required.

Pharmacokinetics of Pinene

Inhalation

α- and β-pinene are insoluble in water yet soluble in blood and adipose tissues. Terpenes indicate high respiratory uptake and accumulation in adipose tissues. Following inhalation the mean blood concentration mainly depends ontime of  exposure . α-pinene and β-pinene have long half-lives, taking more than 2 days for the body to be almost totally clear of them.

 

Boiling Point of Pinene: 311• (F), 155• (C)

When vaping a cannabis strain with pinene one would want to set the temperature of the vape device to about 325″ (F) to get the most benefit from this terpene. Temperatures achieved with smoking should be sufficient to allow full availability of the pinene.

 

Oral Use

A study of volunteers receiving oral α-pinene (9 mg) and studied the metabolic product levels in blood and urine. The maximum blood concentration was reached in 1.6 hours after exposure and the maximum concentration of the urinary α-pinene metabolites was reached 1.6 hours after exposure. The study showed that the blood concentration of orally administrated, unmetabolized α-pinene lasts for a short duration at low concentrations in blood and could be rapidly eliminated from the body unchanged via lungs. Only 22% of the oral dose administrated was detected as metabolites in urine. The amount of α-pinene metabolites found in urine was notably greater compared to blood, with this being indicative of a fast transfer of metabolites from blood to urine with a rapid renal elimination. Detectable metabolite levels and non-detectable α-pinene in blood after low oral doses indicate a fast and approximately entire pre-systemic metabolism, such as hepatic or intestinal first-pass metabolism. However, other pathways of elimination, such as exhaled air, may account for the unknown 78% of the oral dose since only 22% was found in urine.

In summary, α-pinene and β-pinene bioavailability is of short duration at low concentrations, being rapidly metabolized and eliminated from the body due to their volatile nature. 

 

Dermal Application

β-Myrcene, limonene, α-pinene, β-pinene, linalool, geraniol, citronellol, and isomenthone are typical monoterpene constituents of rose oil. In a study investigating the application of rose oil on skin,  α- and β-pinene had different permeability behaviors when they were applied alone compared to as a component in rose oil. When α- and β-pinene were applied alone, permeability was high compared to the other monoterpenes in rose oil. However, when pinene was applied as a component of rose oil, the permeability of α-pinene dropped while the permeability of β-pinene was enhanced. β-pinene was approximately four times higher than that of β-myrcene, limonene, and α-pinene. It is apparent that the skin permeability was positively or negatively affected depending on the presence of other constituents.

Commercial Products

Terpene Products

Commercial terpene products are availabe for use as supplements to be used independently or in combination with cannabis-based products, including THC and CBD.  Some companies promote their products by claiming the constituents in their terpene products are formulated to simulate the same terpene blends of specific cannabis strains.  Upon investigation, it was not possible to find on their website evidence to confirm their claims regarding their blends, probably to protect their proprietary interests. Links to some of these products are available here for educational purposes but are not meant to recommend or endorse the products. It should also be emphasized that these terpene products do not contain THC, CBD or other cannabinoids.

 

CBD Products

In addition to commercial terpene products, there are many CBD products that contain terpenes. CBD products with terpenes are labeled as “broad spectrum” when the constituents have no THC and “full spectrum” when they contain THC at levels up to a 0.3%. Unfortunately, CBD products frequently do not identify their specific terpenes and their concentrations, again, probably to protect their proprietary interests.

See: CBD

 

Resources:

National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

 

www.Healer.com

This website appears to be good resource for exploring medical marijuana.

 

References:

   

Terpenes – Overviews

  1. Therapeutic and Medicinal Uses of Terpenes – 2019
  2. Terpenes:Terpenoids in Cannabis – Are They Important? – 2020
  3. Advances in Pharmacological Activities of Terpenoids – 2020
  4. Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant – 2020
  5. The Cannabis Terpenes – 2020
  6. The “Entourage Effect” – Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders – 2020
  7. Cannabis Essential Oil – A Preliminary Study for the Evaluation of the Brain Effects – 2018
  8. A Systematic Review of Essential Oils and the Endocannabinoid System – A Connection Worthy of Further Exploration – 2020
  9. Efficacy of Essential Oils in Pain – A Systematic Review and Meta-Analysis of Preclinical Evidence – 2021

 

Terpenes – Aromatherapy

  1. Aromatherapy and Aromatic Plants for the Treatment of Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease Clinical Evidence and Possible Mechanisms – 2017
  2. Corrigendum – A question of scent – lavender aroma promotes interpersonal trust -2015
  3. Odors enhance slow-wave activity in non-rapid eye movement sleepOdors enhance slow-wave activity in non-rapid eye movement sleep
  4. Essential Oils and Animals – Which Essential Oils Are Toxic to Pets?
  5. Essential Oils and Pets
  6. Herbs and Their Uses for Animals – Patchouli and Pets
  7. Reactivating memories during sleep by odors – odor specificity and associated changes in sleep oscillations – 2014
  8. Increasing Explicit Sequence Knowledge by Odor Cueing during Sleep in Men but not Women – 2016
  9. Effects of odorant administration on objective and subjective measures of sleep quality, post-sleep mood and alertness, and cognitive performance – 2003
  10. An Olfactory Stimulus Modifies Nighttime Sleep in Young Men and Women – 2005
  11. Massage with or without aromatherapy for symptom relief in people with cancer. – PubMed – NCBI
  12. Aromatherapy hand massage for older adults with chronic pain living in long-term care. – PubMed – NCBI
  13. A Systematic Review of Essential Oils and the Endocannabinoid System – A Connection Worthy of Further Exploration – 2020
  14. Human olfactory receptors – novel cellular functions outside of the nose,” – 2017
  15. The diversified function and potential therapy of ectopic olfactory receptors in non-olfactory tissues – PubMed – 2017
  16. How does your kidney smell? Emerging roles for olfactory receptors in renal function,” – 2017
  17. The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application – 2020
  18. Pharmacology of Natural Volatiles and Essential Oils in Food, Therapy, and Disease Prophylaxis – 2021

 

Terpenes – CB2 Receptor

  1. Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain – an updated review – 2021
  2. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice – 2014
  3. The CB2 receptor and its role as a regulator of inflammation – 2016

 

Terpenes – Synergy with Cannabinoids:

  1. Taming THC – potential cannabis synergy and phytocannabinoid-terpenoid entourage effects – 2011
  2. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  3. Entourage Effect 2.0
  4. Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype – 2018
  5. Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity – 2019
  6. Absence of Entourage – Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Functional Activity of Δ9-THC at Human CB1 and CB2 Receptors – 2019
  7. Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors – 2020
  8. The “Entourage Effect” – Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders – 2020

 

Terpenes – Marijuana Strains

  1. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  2. Terpenoid Chemoprofiles Distinguish Drug-type Cannabis sativa L. Cultivars in Nevada – 2018
  3. Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity – 2019
  4. Identification of Terpenoid Chemotypes Among High (−)-trans-Δ9- Tetrahydrocannabinol-Producing Cannabis sativa L. Cultivars 0 2017
  5. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018

 

Terpenes – Routes of Use:

  1. The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application – 2020
  2. Antiviral effect of phytochemicals from medicinal plants – Applications and drug delivery strategies – 2020
  3. Cannabinoid Delivery Systems for Pain and Inflammation Treatment – 2018

 

Terpenes – Bioavailability

  1. Bioavailability and Pharmacokinetics of Natural Volatile Terpenes in Animals and Humans – 2000
  2. Bioavailability of Bioactive Compounds
  3. SPC Liposomes as Possible Delivery Systems for Improving Bioavailability of the Natural Sesquiterpene β-Caryophyllene – 2018

 

Terpenes – Arthritis

  1. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015

 

Terpenes – Anxiety

  1. Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype – 2018
  2. The “Entourage Effect”: Terpenes Coupled With Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders – PubMed – 2019
  3. Medicinal cannabis for psychiatric disorders – a clinically-focused systematic review – 2020
  4. A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models – 2015
  5. A Systematic Review on the Anxiolytic Effect of Aromatherapy during the First Stage of Labor – 2019
  6. A Systematic Review on the Anxiolytic Effectsof Aromatherapy in People with Anxiety Symptoms – 2011
  7. Anxiolytic Terpenoids and Aromatherapy for Anxiety and Depression – PubMed – 2020
  8. Effect of Aromatherapy on Dental Anxiety Among Orthodontic Patients – A Randomized Controlled Trial – 2019
  9. Essential Oils and Their Constituents – An Alternative Source for Novel Antidepressants – 2017
  10. Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases – 2018
  11. Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia – 2021
  12. The calming effect of roasted coffee aroma in patients undergoing dental procedures – 2021
  13. The Effect of Lavender Aroma on Anxiety of Patients Having Bone Marrow Biopsy- 2020
  14. The-Effects-of-Essential-Oils-and-Terpenes-in-Relation-to-Their-Routes-of-Intake-and-Application-2020
  15. Therapeutic Effect and Mechanisms of Essential Oils in Mood Disorders – Interaction between the Nervous and Respiratory Systems – 2021
  16. Anxiolytic-Like Effects of Bergamot Essential Oil Are Insensitive to Flumazenil in Rats – 2019

 

Terpenes – Infectious Diseases

  1. Phytochemical Analysis and in vitro Antiviral Activities of the Essential Oils of Seven Lebanon Species – 2008
  2. Antiviral effect of phytochemicals from medicinal plants – Applications and drug delivery strategies – 2020
  3. Essential Oils and Coronaviruses – 2020

 

Terpenes – Pain:

  1. Analgesic-like Activity of Essential Oils Constituents – 2011
  2. Analgesic-Like Activity of Essential Oil Constituents – An Update – 2017
  3. Medicinal Plants of the Family Lamiaceae in Pain Therapy – A Review – 2018
  4. Analgesic Potential of Essential Oils – 2016
  5. Medicinal Plants of the Family Lamiaceae in Pain Therapy – A Review – 2018
  6. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  7. Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant – 2020
  8.  The Molecular Mechanisms That Underpin the Biological Benefits of Full-Spectrum Cannabis Extract in the Treatment of Neuropathic Pain and Inflammation – PubMed – 2020
  9. Cannabis-based medicines and the perioperative physician – 2019
  10. Cannabis‐based medicines for chronic neuropathic pain in adults – 2018
  11. Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain – An Update on Current Evidence and Cannabis Science – 2018
  12. Role of Cannabinoids and Terpenes in Cannabis-Mediated Analgesia in Rats – PubMed – 2019
  13. Antinociceptive effect of inhalation of the essential oil of bergamot in mice – 2018
  14. Analgesic Potential of Essential Oils – 2016
  15. Analgesic-Like Activity of Essential Oil Constituents – An Update – 2017

 

 

Terpenes – Headaches:

  1.  Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain – An Update on Current Evidence and Cannabis Science – 2018
  2. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018

 

Terpenes – Inflammation:

  1. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015 
  2. Cannabis sativa L. and Nonpsychoactive Cannabinoids – Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer – 2018
  3. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  4. Therapeutic Potential of Volatile Terpenes and Terpenoids from Forests for Inflammatory Diseases – 2020
  5.  The Molecular Mechanisms That Underpin the Biological Benefits of Full-Spectrum Cannabis Extract in the Treatment of Neuropathic Pain and Inflammation – PubMed – 2020
  6. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015
  7. Cannabis, Cannabinoids, and the Endocannabinoid System—Is there Therapeutic Potential for Inflammatory Bowel Disease? – 2019
  8. Therapeutic Applications of Terpenes on Inflammatory Diseases – 2021

 

Esssential Oils

 

Essential Oils – Overviews

  1. Essential Oils, Part I Introduction – PubMed – 2016
  2. Essential Oils, Part II General Aspects – PubMed – 2016
  3. Essential Oils, Part III Chemical Composition – PubMed – 2016
  4. Essential Oils, Part IV Contact Allergy – PubMed- 2016
  5. Essential Oils, Part V Peppermint Oil, Lavender Oil, and Lemongrass Oil – PubMed 2016

 

 

Essential Oils – Bearded Irises

  1. Identification of Floral Scent Profiles in Bearded Irises – 2019

 

 

Essential Oils – Bergamot

  1. The Anxiolytic Effect of Aromatherapy on Patients Awaiting Ambulatory Surgery – A Randomized Controlled Trial – 2013
  2. Antinociceptive effect of inhalation of the essential oil of bergamot in mice – 2018
  3. Anxiolytic-Like Effects of Bergamot Essential Oil Are Insensitive to Flumazenil in Rats – 2019
  4. Bergamot – Natural Medicines – Professional.pdf
  5. Citrus bergamia essential oil – from basic research to clinical application – 2015
  6. Role of 5-HT1A Receptor in the Anxiolytic-Relaxant Effects of Bergamot Essential Oil in Rodent – 2020 Neuropharmacological Properties of the Essential Oil of Bergamot for the Clinical Management of Pain-Related BPSDs – PubMed – 2019
  7. Possible involvement of the peripheral Mu-opioid system in antinociception induced by bergamot essential oil to allodynia after peripheral nerve injury – PubMed – 2018
  8. Peripherally injected linalool and bergamot essential oil attenuate mechanical allodynia via inhibiting spinal ERK phosphorylation – PubMed – 2013
  9. Neuropharmacology of the essential oil of bergamot – PubMed – 2010
  10. Effect of Harvesting Time on Volatile Compounds Composition of Bergamot (Citrus × Bergamia) Essential Oil – 2019
  11. Chemical Composition and Biological Activities of Essential Oils from Peels of Three Citrus Species – 2020
  12. Chemical_Composition_of_Bergamot_Citrus_Bergamia_Risso_Essential_Oil_Obtained_by_Hydrodistillation – 2010
  13. Cannabinoid Signaling in the Skin – Therapeutic Potential of the “C(ut)annabinoid” System – 2019
  14. Rational Basis for the Use of Bergamot Essential Oil in Complementary Medicine to Treat Chronic Pain – PubMed – 2016

 

Essential Oils – Plumeria

  1. Constituents of essential oils from the leaf and flower of Plumeria alba grown in Nigeria – PubMed – 2014

 

Individual Terpenes

Terpenes: β-Caryophyllene:

  1. (−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis – 2017
  2. Antiallodynic effect of β-caryophyllene on paclitaxel-induced peripheral neuropathy in mice. – PubMed – NCBI
  3. Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion – 2018
  4. Antiallodynic effect of β-caryophyllene on paclitaxel-induced peripheral neuropathy in mice. – PubMed – NCBI
  5. Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation? – 2016
  6. The anxiolytic-like effect of an essential oil derived from Spiranthera odoratissima A. St. Hil. leaves and its major component, β-caryophyllene, in male mice – 2012
  7. β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties – 2016
  8. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice – 2014
  9. Toxicological Evaluation of β-Caryophyllene Oil: Subchronic Toxicity in Rats. – PubMed – NCBI 2016
  10. The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic… – PubMed – NCBI – 2014
  11. The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain – 2013
  12. SPC Liposomes as Possible Delivery Systems for Improving Bioavailability of the Natural Sesquiterpene β-Caryophyllene – 2018
  13. β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway – 2011
  14. Why wild giant pandas frequently roll in horse manure – 2020
  15. Beta-caryophyllene is a dietary cannabinoid – 2008
  16. Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. – 2006
  17. The menthol receptor TRPM8 is the principal detector of environmental cold – PubMed – 2007
  18. Molecular basis of peripheral innocuous cold sensitivity – 2018
  19. Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception – PubMed – 2013
  20. NON-CANNABIS THERAPY – Cannabinoid Therapy Without Using Cannabis: Direct Effects™ Topical β-Caryophyllene
  21. Beta-caryophyllene enhances wound healing through multiple routes – 2019
  22. Preparation and Characterization of Liposomal β‐Caryophyllene (Rephyll) – 2020

 

Terpenes: Linalool:

  1. GS12-linalool
  2. Linalool – 1997
  3. The “Entourage Effect”: Terpenes Coupled With Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders – PubMed – 2020
  4. An olfactory stimulus modifies nighttime sleep in young men and women. – PubMed – NCBI
  5. Lavender and sleep – A systematic review of the evidence – 2012
  6. Lavender and the Nervous System – 2013
  7. Effects of odorant administration on objective and subjective measures of sleep quality, post-sleep mood and alertness, and cognitive performance – 2003
  8. In-vitro inhibition of human erythrocyte acetylcholinesterase by salvia lavandulaefolia essential oil and constituent terpenes. – PubMed – NCBI – 2000
  9. Odors enhance slow-wave activity in non-rapid eye movement sleep – 2016
  10. A question of scent – lavender aroma promotes interpersonal trust – 2015
  11. Is Lavender an Anxiolytic Drug? A Systematic Review of Randomised Clinical Trials – 2012
  12. Efficacy of Silexan in subthreshold anxiety – meta-analysis of randomised, placebo-controlled trials – 2019
  13. Essential oil of lavender in anxiety disorders – Ready for prime time? – 2017
  14. Linalool is a PPAR ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome – 2014
  15. A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health – Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis – 2021
  16. The Efficacy of Lavender Aromatherapy in Reducing Preoperative Anxiety in Ambulatory Surgery Patients Undergoing Procedures in General Otolaryngology – 2017
  17. Efficacy, Safety and Tolerability of Aroma Massage with Lavender Essential Oil – an Overview – 2020
  18. Antinociceptive and anticonvulsant effects of the monoterpene linalool oxide – 2017
  19. Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia) Essential Oil on Central Nervous System Targets – 2017
  20. Linalool Ameliorates Memory Loss and Behavioral Impairment Induced by REM-Sleep Deprivation through the Serotonergic Pathway – 2018
  21. Effects of lavender on anxiety, depression and physiologic parameters – Systematic Review and Meta-Analysis – 2021
  22. Lavender and sleep – A systematic review of the evidence – 2012
  23. Lavender and the Nervous System – 2013
  24. A question of scent – lavender aroma promotes interpersonal trust – 2015

 

 

Terpenes, Linalool: – Silexan

  1. A Multi-Center, Double-Blind, Randomised Study of the Lavender Oil Preparation Silexan in Comparison to Lorazepam for Generalized Anxiety Disorder – 2010
  2. Is Lavender an Anxiolytic Drug? A Systematic Review of Randomised Clinical Trials – 2012
  3.  An Orally Administered Lavandula Oil Preparation (Silexan) for Anxiety Disorder and Related Conditions- An Evidence Based Review – 2013
  4. Lavender oil preparation Silexan is effective in generalized anxiety disorder – a randomized, double-blind comparison to placebo and paroxetine – 2014
  5. Silexan in anxiety disorders – Clinical data and pharmacological background – 2017
  6. Effectiveness of Silexan Oral Lavender Essential Oil Compared to Inhaled Lavender Essential Oil Aromatherapy for Sleep in Adults- A Systematic Review – 2018
  7. Silexan in anxiety disorders Clinical data and pharmacological background – PubMed – 2018
  8. Efficacy and safety of lavender essential oil (Silexan) capsules among patients suffering from anxiety disorders – A network meta-analysis – 2019
  9. Efficacy of Silexan in subthreshold anxiety – meta-analysis of randomised, placebo-controlled trials – 2019
  10. Therapeutic effects of Silexan on somatic symptoms and physical health in patients with anxiety disorders – A meta- analysis – 2020
  11. Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of ‘subsyndromal’ anxiety disorder a randomized, double-blind, placebo controlled trial – PubMed – 2010
  12. A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder – PubMed – 2009
  13. No Abuse Potential of Silexan in Healthy Recreational Drug Users – A Randomized Controlled Trial – 2021

 

Terpenes – Limonene

  1. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015
  2. Neuroprotective Potential of Limonene and Limonene Containing Natural Products – 2021

 

Terpenes: Myrcene

  1. β-MYRCENE – IARC MONOGRAPHS
  2. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. – 2015
  3. Myrcene—What Are the Potential Health Benefits of This Flavouring and Aroma Agent? – 2021

 

Terpenes: Pinene

  1. A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health – Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis – 2021
  2. Therapeutic Potential of α- and β-Pinene – A Miracle Gift of Nature – 2019

 

 

Medical Marijuana – Product Evaluation

  1. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018
  2. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
  3. Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements – 2020

 

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

For more information, please contact Accurate Clinic.

 

Supplements recommended by Dr. Ehlenberger may be purchased commercially online or at Accurate Clinic.

Please read about our statement regarding the sale of products recommended by Dr. Ehlenberger.

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