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- 1. Cannabis Associate Prof. Jilan A. Nazeam Pharmacognosy department, October 6 University Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world.
- 2. Content – Definition – History – Route of administration – Extraction – Composition – Mechanism – Therapeutic effects – Diagnosis – Toxicity – Pharmacokinetics – Tests – Stories/ case study – Hydro ..
- 3. Defination
- 4. Comes from one of two plants: Cannabis sativa Cannabis indica WhatisCannabis? Cannabis has taken scientists on a journey to a better understanding of the human body,
- 5. Colder environments and higher altitudes like Mountains Short and thick; darker green Lower THC:CBD Sleepiness and relaxation Warm countries like Thailand, Asia, Mexico Tall and thin; lighter green Higher THC:CBD Stimulation, euphoria, focus, creativity, and imagination
- 8. CANNABIS SATIVA Product: Marijuana, Hashish, Hashish oil, Cannabis sativa, Delta-9- tetrahydrocannabinol Street Name: Pot, grass, weed, joint, ganja, hash
- 9. Forms: O Marijuana (dried leaves, stems, flowering tops) Schedule I drug Consumption: commonly in rolled cigarettes and hollowed cigars, also orally o Hashish (relatively pure resin or leaf extracts) Consumption: smoked or eaten Potency depends on preparation Hash oil = alcoholic extract, highly potent
- 10. History
- 11. Bhang is a brewed tea from cannabis and is often referred to in Indian culture during festivals Festival of Holi (Festival of Colors) quickly, cannabis became entrenched into Sumerian religion because they believed it was putting them in touch with their gods. The first recorded use of cannabis as a drug was about 2,700 B.C., in China. The Chinese called it “the drug that takes away the mind” –
- 12. It was introduce to Europe in early 19th century by Napoleon's army returning from Egypt, and later in the same century to Britain for medical use by surgeon who served in India.
- 13. 1960s CBD and THC were first extracted from cannabis. Their structures and stereochemistry were elucidated in Raphael Mechoulam’s laboratory. Twenty years later In 1965 Mechoulam’s lab synthesized both compounds. Since then, more than 100 cannabinoids have been catalogued. several animal studies showed that CBD had activity against epilepsy 1970s “We knew quite a lot about the effects of THC but didn’t know how it exerted its effects,” explained Mechoulam in an interview at the 13th European Congress on Epileptology. “People thought it had a general effect. It turns out that was wrong.” 1980s Findings from Allyn Howlett’s lab at St. Louis University provided solid evidence for the existence of cannabinoid receptors.
- 14. Howlett’s group used new technique (radiolabeling) that allowed the recognition sites of receptors to be detected. Found that there were high-affinity binding sites— otherwise known as receptors—in rat brain membranes. Cannabinoid 1 (CB1) receptor discovered Mechoulam’s lab isolated the first endocannabinoid: a molecule that was ultimately classified as a CB1 receptor partial agonist. It was identified as anandamide. Soon after, the lab isolated another endocannabinoid, 2- arachidonoylglycerol, or 2-AG. By 1988 In 1990 A second cannabinoid receptor (CB2) identified. In 1993 In 1992 Regulators, modulators, healers “One of the major effects of endogenous cannabinoids is to regulate the release of dopamine, serotonin, and other neurotransmitters,” said Mechoulam. “They seem to be major regulators.”
- 15. Endocannabinoids are formed on demand, when and where needed; they are released from the postsynaptic neuron and act presynaptically. Since their discovery, endocannabinoids have been found to play a role in memory, Mood, Appetite Metabolism, Sleep, Pain response, Thermoregulation Immunity. The system also appears to regulate reproduction; the developing embryo expresses cannabinoid receptors that are responsive to anandamide secreted in the uterus
- 22. Extractions
- 26. • Male and female plants separated. • Female contain highest concentration of THC. • Flowering top has highest THC concentration. MARIJUANA: Prepared from dried flowering tops and leave of plant. O THC concentration 0.5- 5%. MARIJUANA HASHISH ( Hash or charas): consist of dried cannabis resin. • Light brown to almost black color. O THC concentration 5-8%. HASH OIL: it obtained by extracting THC from Hasish or Marijuana in oil. • Clear pale yellow / green to brown black colour. O THC concentration 15-30%. GANJA: Buds and flowering top of female plant. BHANG: Cut and dried large leaves & stem of plants. PREPARATION OF CANNABIS
- 31. Psychoactive organic compound Affect CNS Molecular formula: C21H30O2 (delta-9-THC) Molecular weight: 314.4 g/mol What is THC
- 38. Medical Cannabis – Potential therapeutic uses: – Chemotherapy-induced nausea and vomiting – Multiple sclerosis – Chronic pain – Anxiety and depression – Sleep disorders – Inflammation – Irritable bowel syndrome – Used for conditions like cancer, AIDS, epilepsy, glaucoma
- 39. MARINOL Marinol, a synthetic form of THC, was first approved by the Food and Drug Administration (FDA) in 1985 as an anti- emetic (against nausea or vomitting) for chemotherapy patients and then in 1993 as an appetite stimulant for AIDS patients. Synthetic forms of marijuana exist, more incidents in US than BC Spice, can cause death
- 40. a seizure medication that is prescribed by a physician. a plant-based formulation of cannabidiol (CBD) that is prescribed as an oral solution (liquid). • CBD is also the first ever FDA approved medication to treat seizures. EPIDIOLEX
- 41. Toxicity
- 42. • Most young people use cannabis in order to experience a "high," characterized by Feelings of mild euphoria, Relaxation CANNABIS INTOXICATION
- 45. Marijuana smoke contains many of the same toxins, carcinogens and irritants as cigarette smoke • Leaves more tar in lungs than cigarette smoke • Causes respiratory problems such as: Bronchitis (chronic and acute) Persistent cough - Wheezing • Increased heart rate
- 46. loss of sexual power Brain damage Heart trouble Nosebleeds loss of appetite (daily/weekly use that continues over weeks/months/years): Bronchitis Respiratory Failure Mental/ Physical / Psychological / Psychosocial disorder
- 47. Ø Schizophrenia (Early use and heavy use) Ø Tremors Ø Severe depression Ø Acute psychosis, suicidality (Dose dependent) Ø Bi-phasic effect on mood and anxiety Brain damage Heart trouble Ø Acute increases in heart rate Ø Increase blood pressure Ø Increase risk of angina Cognitive funcation § Poor academic performance § Impairment to memory, &intelligence § Impairment to decision making § Impairment recall & learning § Loss of IQ points
- 48. Female: THC interfere with the hormones controlled by the hypothalamic- pituitary-gonadal axis, delaying oestrous and ovulation Effects on libido (dose dependent) Studies support that lower doses improve desire but higher doses either lower desire or do not affect desire at all. prolonging orgasm (one study showed that it inhibit the orgasm) Male: Ø Lowered testosterone levels Ø Retarded sperm maturation Ø Reduced sperm count Ø Inhibit sperm motility and funcation Ø Possible link to testicular cancer Ø Decrease LH hormones Ø Decreased fetal growth Pregnancy Ø Increased risk of premature birth/ Ø Postnatal neurodevelopmental issues loss of sexual power
- 51. Latif, Z. and Garg, N., 2020. The impact of marijuana on the cardiovascular system: a review of the most common cardiovascular events associated with marijuana use. Journal of clinical medicine, 9(6), p.1925.
- 55. The acute toxicity of cannabinoids is said to be low and there is little public awareness of the potentially hazardous cardiovascular effects of cannabis, e.g. marked increase in heart rate or supine blood pressure. We describe the cases of two young, putative healthy men who died unexpectedly under the acute influence of cannabinoids. To our knowledge, these are the first cases of suspected fatal cannabis intoxications where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical and genetical examinations, were carried out. The results of these examinations are presented. After exclusion of other causes of death we assume that the young men experienced fatal cardiovascular complications evoked by smoking cannabis.
- 61. Marijuana IS Addictive • Use can lead to dependence and addiction Dependence⇒ when the brain adapts to large amounts of marijuana by reducing production of and sensitivity to its own endocannabinoid neurotransmitters. Addiction → when a person cannot stop using marijuana even though it interferes with many aspects of his or her life. • More likely for youth who use frequently, start using at a younger age, and use for longer periods of time - Daily youth users⇒ 50% at risk Frequent users experience withdrawal symptoms - Physical symptoms Blunted dopamine response
- 62. MEDICINAL OR MISUSED ????????? • TCH exposure has developmental consequences: affects cognitive abilities/IQ if used regularly in teens. • Children exposed to marijuana in the womb have an increased risk of problems with attention, memory, and problem-solving. • Not "addictive" (induces withdrawal symptoms) but people can become dependant. Augment schizophrenic tendencies Drugs, including cannabis, can impair your ability to drive by: • Affecting motor skills • Slowing reaction time • Impairing short-term memory and concentration • Causing drivers to vary speed and to wander, and • Reducing the ability to make decisions quickly.
- 67. – The median lethal dose of THC in humans is not fully known as there is conflicting evidence. – Some rats died within 72 hours after a dose of up to 3600 mg/kg. – A 2014 study gave the median lethal dose in humans at 30 mg/kg (2.1 grams THC for a person who weighs 70 kg), observing cardiovascular death in otherwise healthy subjects. – A different 1972 study gave the median lethal dose for intravenous THC in mice and rats at 30–40 mg/kg.
- 68. Drug Interactions Warfarin THC and CBD increase warfarin levels Frequent cannabis use associated with increased INR Theophylline THC decreases theophylline levels Clobazam CBD increases clobazam levels Additive CNS depressant effects Alcohol Barbiturates Benzodiazepines
- 69. Diagnosis
- 70. History Collection/ MSE & Physical Examination Urine test can usually identified metabolite of cannabinoids. Urine test can usually identified metabolite of cannabinoids, 11- hydroxy A-9 THC. • Because they are fat soluble, remain in body for extended period. O Individual who are chronic users of cannabinoids may show +ve urine test for 2-4 week after using. It can also detect in head hair, pubic hair, urine, sweat, saliva and blood of users.
- 71. – The main metabolite excreted in the urine is 11-nor-9-tetrahydrocannabinol- 9- carboxylic acid (9-THC-COOH). – – The THC Rapid Test (Urine) is a rapid urine screening test that can be performed without the use of an instrument. – The test utilizes a monoclonal antibody to selectively detect elevated levels of Marijuana in urine.
- 72. THC and its 11-OH-THC and THC-COOH metabolites can be detected and quantified in blood, urine, hair, oral fluid or sweat using a combination of immunoassay and chromatographic techniques as part of a drug use testing program or in a forensic investigation.[ There is ongoing research to create devices capable of detecting THC in breath.[
- 73. Immunoassay An immunoassay is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody or an antigen.
- 74. Detection and confirmation of drug use of cannabis/marijuana and to specifically identify and quantify delta-8-carboxy tetrahydrocannabinol (THC- COOH) and delta-9-THC-COOH METHOD NAME Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
- 75. Detection and confirmation of drug use of cannabis/marijuana and to specifically identify and quantify delta-8-carboxy tetrahydrocannabinol (THC- COOH) and delta-9-THC-COOH METHOD NAME Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
- 77. Treatment
- 78. CANNABIS WITHDRAWAL Cessation of the use in daily cannabis user results in withdrawal symptom. • Appear within 24 hours, most marked within 10 days and may persist up to 28 days. • Irritability, anger, or aggression. Nervousness or anxiety. • Sleep difficulty (e.g., insomnia, disturbing dreams). Decreased appetite or weight loss. Restlessness. Depressed mood. Physical symptoms causing significant discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache. • Fatigue, difficulty in concentration etc..
- 79. CANNABIS WITHDRAWAL The stomach is evacuated and the patient treated symptomatically. Antidepressant; • Diazepam 0.1 mg/kg orally helps to control excitement and convulsions. • Benzodiazepines prescribe medication.are most commonly Buspiron (up to 60 mg/ day) for 12 week is 1* choice.
- 84. Criminal Case Studies Involving Forensic Toxicology Case Study #3: Drug Overdose or Intentional Poisoning – That is the Question Late one evening, a tenant of a three-storey rooming house called police. The tenant had discovered the body of a 26-year-old male when he entered the man’s suite to borrow some cigarettes. The male subject, known to police as a low-level drug dealer who frequented the seedier parts of the downtown core, appeared as if he had died of a drug overdose. After police arrived and sealed off the subject’s suite, they noticed that the subject’s eyes were wide open and that rigor mortis had already set in. The subject’s legs and left arm were oriented at strange angles—almost perpendicular to his torso. That the subject had thrashed about the room during his last moments or that he had been involved in a struggle, seemed evident. Police found several marijuana cigarettes, residue from what appeared to be crack cocaine, and two empty bottles of prescription barbiturates scattered around the subject’s body. A suicide note was found nearby. Unfortunately, police were unable to find a suitable writing sample from the subject. Consequently, the authorship of the note could not be confirmed. In addition, an empty bottle of rat poison was found in a dumpster outside the rooming house. No fingerprints were found on the bottle. ﻓ ﻲ و ﻗ ت ﻣ ﺗ ﺄ ﺧ ر ﻣ ن إ ﺣ د ى ا ﻷ ﻣ ﺳ ﯾ ﺎ ت ، ا ﺗ ﺻ ل ﻣ ﺳ ﺗ ﺄ ﺟ ر ﻣ ﻧ ز ل ﻣ ﻛ و ن ﻣ ن ﺛ ﻼ ﺛ ﺔ ط و ا ﺑ ق ﺑ ﺎ ﻟ ﺷ ر ط ﺔ . و ﻛ ﺎ ن ا ﻟ ﻣ ﺳ ﺗ ﺄ ﺟ ر ﻗ د ا ﻛ ﺗ ﺷ ف ﺟ ﺛ ﺔ ر ﺟ ل ﯾ ﺑ ﻠ ﻎ ﻣ ن ا ﻟ ﻌ ﻣ ر 26 ﻋ ﺎ ﻣ ﺎ ﻋ ﻧ د ﻣ ﺎ د ﺧ ل ﺟ ﻧ ﺎ ح ا ﻟ ر ﺟ ل ﻻ ﺳ ﺗ ﻌ ﺎ ر ة ﺑ ﻌ ض ا ﻟ ﺳ ﺟ ﺎ ﺋ ر . و ﺑ د ا ا ﻟ ذ ﻛ ر ا ﻟ ذ ي ﻋ ر ﻓ ﺗ ﮫ ا ﻟ ﺷ ر ط ﺔ ﺑ ﺄ ﻧ ﮫ ﺗ ﺎ ﺟ ر ﻣ ﺧ د ر ا ت ﻣ ﻧ ﺧ ﻔ ض ا ﻟ ﻣ ﺳ ﺗ و ى ﯾ ﺗ ر د د ﻋ ﻠ ﻰ ا ﻷ ﺟ ز ا ء ا ﻷ ﻛ ﺛ ر ﺑ ذ ا ر ة ﻓ ﻲ ﻗ ﻠ ب و ﺳ ط ا ﻟ ﻣ د ﯾ ﻧ ﺔ ﻛ ﻣ ﺎ ﻟ و أ ﻧ ﮫ ﻣ ﺎ ت ﺑ ﺳ ﺑ ب ﺟ ر ﻋ ﺔ ز ا ﺋ د ة ﻣ ن ا ﻟ ﻣ ﺧ د ر ا ت . ﺑ ﻌ د و ﺻ و ل ا ﻟ ﺷ ر ط ﺔ و إ ﻏ ﻼ ق ﺟ ﻧ ﺎ ح ا ﻟ ﺷ ﺧ ص ، ﻻ ﺣ ظ و ا أ ن ﻋ ﯾ و ن ا ﻟ ﺷ ﺧ ص ﻛ ﺎ ﻧ ت ﻣ ﻔ ﺗ و ﺣ ﺔ ﻋ ﻠ ﻰ ﻣ ﺻ ر ا ﻋ ﯾ ﮭ ﺎ و أ ن ا ﻟ ﻣ و ت ا ﻟ ﺻ ﺎ ر م ﻗ د ﺗ م ﺿ ﺑ ط ﮫ ﺑ ﺎ ﻟ ﻔ ﻌ ل
- 85. While canvassing other tenants in the rooming house, police spoke with an acquaintance of the subject who mentioned that two unidentified males who seemed to think that the subject had cheated them in a drug deal had recently threatened him. A thorough search of the subject’s one-room suite by police produced a used syringe from a garbage can in the suite. To determine the cause of death, an autopsy was conducted by the medical examiner who noted a small puncture wound in the subject’s right upper arm. A forensic toxicologist made a chromatogram (sample evidence #2) from a sample of the victim’s blood. Use the above information and the following images to answer the questions in your assignment. أ ﺛ ﻧ ﺎ ء ا ﺳ ﺗ ط ﻼ ع آ ر ا ء ا ﻟ ﻣ ﺳ ﺗ ﺄ ﺟ ر ﯾ ن ا ﻵ ﺧ ر ﯾ ن ﻓ ﻲ ﻣ ﻧ ز ل ا ﻟ ﻐ ر ﻓ ﺔ ، ﺗ ﺣ د ﺛ ت ا ﻟ ﺷ ر ط ﺔ ﻣ ﻊ أ ﺣ د ﻣ ﻌ ﺎ ر ف ا ﻟ ﻣ و ﺿ و ع ا ﻟ ذ ي ذ ﻛ ر أ ن ر ﺟ ﻠ ﯾ ن ﻣ ﺟ ﮭ و ﻟ ﯾ ن ﯾ ﺑ د و أ ﻧ ﮭ ﻣ ﺎ ﯾ ﻌ ﺗ ﻘ د ا ن أ ن ا ﻟ ﺷ ﺧ ص ا ﻟ ﻣ ﻌ ﻧ ﻲ ﻗ د ﺧ د ﻋ ﮭ ﻣ ﺎ ﻓ ﻲ ﺻ ﻔ ﻘ ﺔ ﻣ ﺧ د ر ا ت ﻗ د ھ د د ا ه ﻣ ؤ ﺧ ر ا . أ د ى ا ﻟ ﺗ ﻔ ﺗ ﯾ ش ا ﻟ ﺷ ﺎ ﻣ ل ﻟ ﺟ ﻧ ﺎ ح ا ﻟ ﺷ ﺧ ص ا ﻟ ﻣ ﻛ و ن ﻣ ن ﻏ ر ﻓ ﺔ و ا ﺣ د ة ﻣ ن ﻗ ﺑ ل ا ﻟ ﺷ ر ط ﺔ إ ﻟ ﻰ إ ﻧ ﺗ ﺎ ج ﺣ ﻘ ﻧ ﺔ ﻣ ﺳ ﺗ ﻌ ﻣ ﻠ ﺔ ﻣ ن ﻋ ﻠ ﺑ ﺔ ﻗ ﻣ ﺎ ﻣ ﺔ ﻓ ﻲ ا ﻟ ﺟ ﻧ ﺎ ح . ﻟ ﺗ ﺣ د ﯾ د ﺳ ﺑ ب ا ﻟ و ﻓ ﺎ ة ، ﺗ م إ ﺟ ر ا ء ﺗ ﺷ ر ﯾ ﺢ ﻟ ﻠ ﺟ ﺛ ﺔ ﻣ ن ﻗ ﺑ ل ا ﻟ ط ﺑ ﯾ ب ا ﻟ ﺷ ر ﻋ ﻲ ا ﻟ ذ ي ﻻ ﺣ ظ و ﺟ و د ﺟ ر ح ﺛ ﻘ ب ﺻ ﻐ ﯾ ر ﻓ ﻲ ا ﻟ ﺟ ز ء ا ﻟ ﻌ ﻠ و ي ا ﻷ ﯾ ﻣ ن ﻣ ن ا ﻟ ﺷ ﺧ ص ا ﻟ ﻣ ﻌ ﻧ ﻲ .
- 86. Sample Evidence #1: Chromatogram of Victim’s Blood Chromatogram of Various Drugs and Poisons