Cannabis Flashcards

1
Q

The Cannabis plant

A
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2
Q

From a “drug” point of view, what are the important aspects of the cannabis plant

A

From a “drug” point of view the important aspects of cannabis plant are flowering or fruiting tops and leaves

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3
Q

What can also be extracted and where can this be extracted from?

A

Excreted resin can also be extracted from trichomes (hairs) which are most abundant on the flower heads and surrounding leaves of the mature female plant

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4
Q

What are the important aspects of the cannabis plant that contain relative content of cannabinoids

A
  • From an actual “drug” POV important aspects of cannabis plant are relative content of cannabinoids, especially ∆9-THC (delta-9-tetrahydrocannabinol)- present in the plant tops and resin
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5
Q

About 120 phytocannabinoids recorded in Cannabis sativa L. (Linneus) belonging to 11 chemical types:

A

**1. (-)-trans-∆9-Tetrahydrocannabinol (∆9-THC): INTOXICATING
2. (-)-trans-∆8-Tetrahydrocannabinol (∆8-THC): INTOXICATING **
3. Cannabigerol (CBG)
4. Cannabichromene (CBC)
5. Cannabidiol (CBD): NOT INTOXICATING
6. Cannabinodiol (CBND)
7. Cannabielsoin (CBE)
8. Cannabicyclol (CBL)
9. Cannabinol (CBN)
10. Cannabitriol (CBT)
11. Miscellaneous types

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6
Q

What are Phytocannabinoids derived from?

A

Phytocannabinoids are cannabinoids derived from the cannabis plant. The phytocannabinoids are most concentrated in the glandular trichomes (hairy outgrowths) of the flowering heads of the female plant

Phytocannabinoids derive from** CBGA or CBGV**

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7
Q

What are Neutral cannabinoids derivced from?

A

Neutral cannabinoids (CBD, ∆9-THC, CBG, etc.) derive from decarboxylation of their gerolic acid carboxylic acid precursors (i.e., CBDA, THCA, CBCA)

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8
Q

What is Decarboxylation triggered by?

A

heat and/or light

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9
Q

How is THC made?

A
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10
Q

What can ∆9-THC isomerise to?

A

∆9-THC can isomerise to the more stable ∆8-THC (intoxicant as well)- need chromatography to distinguish between ∆9 and ∆8 THC

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11
Q

What is a fibre-type cannabis and a drug-type cannabis?

A
  • (∆9-THC+CBN)/CBD<1= fibre-type cannabis
  • (∆9-THC+CBN)/CBD>1= drug-type cannabis

Drug-type and fiber-type cannabis are classified based on the ratio of THC to CBD, which is mainly attributed to differences in the gene sequences encoding the enzymes involved in cannabinoid biosynthetic pathways

On the basis of the THC content all cannabis plants are divided into fibre-type and drug-type plants. The fibre-type plant does not exceed 0.4% of THC while the drug-type plant usually contains up to 5% of THC, though higher percentages (up to 10%) have been reported

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12
Q

What are the different types of cannabis plant?

A
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13
Q

Cannabis sativa L. (Linneus) has 2 sub species, what is the ∆9-THC content of each?

A
  • Cannabis sativa L. subsp. Sativa ∆9-THC <0.3%, grown for fibres and oil
  • Cannabis sativa L. subsp. Indica ∆9-THC >1%, intoxicant properties
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14
Q

How many varieties of sativa subspecies are there?

A

1

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15
Q

How many varieties of indica subspecies are there?

A

3

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16
Q

Which cannabis plant is most likely used from a drug perspective?

A

Indica has has the highest THC content

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17
Q

How mant subspecies of ruderalis are there?

A

Cannabis ruderalis (low level THC) considered to be own species by some or a further subspecies of cannabis sativa L.

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18
Q

How does the THC content vary within the cannabis plant?

A
  • Pistillate flowers: 10-12% ∆9-THC
    o Leaves 1-2%
    o Stalks: 0.1-0.3%
    o Roots: <0.03%
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19
Q

Can the THC rough % vary in the cannabis plant?

A

Can be influenced by genetics, cultivation and climatic conditions

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20
Q

What are the various names that refer to products from part of plant and associated extract?

A

marijuana, dope, grass, skunk, weed, pot, ganja, hashish, hash, herb, dagga, spliff, kif, etc

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21
Q

What is marijuana referring to?

A

Marijuana, in the strict sense, refers to most parts of the plant, whether growing or not, the seeds, and the resin extracted but does not include the fibre produced from the mature stalks, or oils or cake produced from the seeds. Often the term is used to describe the dried and crushed flower heads and small leaves of the cannabis plant (‘grass’)

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22
Q

Tell me about the preparation ‘sinsemilla

A

The preparation **‘sinsemilla’ **consists of flower tops collects from plants grown in a pollen-free environment and because these are unfertilised there are no seeds, produced more cannabinoids

Sinsemilla, which is both important and home grown, is most commonly produced by intensive indoor cultivation methods. ‘Skunk’ is a form of sinsemilla with high THC content

23
Q

Tell me about Hashish or hash
What is it referring to?
The colour and texture?
How it is made?

A

* Hashish or hash typically refers to the resin alone, being derived from the Arabic ‘hashish al kief’ meaning dried herb or pleasure

  • The colour and texture of the resin varies depending on the geographical origin, source and purity, such as yellow in colour from the middle east (Middle east, such as Morocco and Lebanon) or brown or black from Pakistan and Afghanistan
  • The trichomes, are separated from the plant by mechanical means of grinding and sieving or alternatively by agitating in iced water and then filtering through increasing fine sieves or bags
  • The resulting powder is compressed into blocks of hashish aided by heat
  • If the powder is not compressed, the dry trichomes are often referred to as ‘kief’ instead of ‘hashish’
24
Q

How is hash oil prepared
Whats the THC content of hash oil?

A
  • Hash oil is prepared by chemically extraction of the plant using a solvent such as ethanol (tincture), butane (butane hash oil, BHO) or propane to dissolve the lipophilic desirable resin. The remaining plant material is then filtered out of the solution and sent to the compost. The solvent is then evaporated, leaving behind the hash oil
  • Solidified oil can be broken up in pieces to be used (“shatter”). Liquid form used for “dabbing”
  • Hash oil contains well over 60% THC. Increased use of hash oil, especially in USA
25
Q

Tell me about Cannabis edibles

A

Cannabis edible are various products (e.g., sweets/ candy, baked products- cakes, cookies, chocolate, drink, etc) containing cannabis material (notionally low %THC)

26
Q

Cannabis: global stats

A
27
Q

Cannabis: global stats

A
28
Q

Cannabis: US stats

A
29
Q

Annual self-reporting user survey

A
30
Q

What are the different routes of administration?

A
  • Inhalation/ smoking
  • Ingestion
31
Q

Tell me about the inhalation/smoking administration of cannabis

A

o In Europe, Australia and the Americans, cannabis is usually smoked, being rolled in cigarette rolling paper, termed a spliff or joint (the other term was reefer), or the smoke draw through bongs or pipes

o The loose herbal material burns relatively easily and may be smoked pure or often mixed with tobacco as a bulking agent for titrating the dose and to help the joint burn smoothly

o Hashish does not burn easily and also because the amount required to produce intoxication is quite small, it is usually crumbled for mixing with tobacco

o The oil, which is thick, may be smeared across cigarette rolling paper and then rolled with tobacco, or the oil placed on a hot knife that is then held under the nose so that the fumes can be inhaled

o “dabbing” rigs used for heating of hash oil liquid for inhalation

32
Q

Tell me about the ingestion route of administration for cannabis

A

o In India, the Middle East and North Africa, it is a tradition to take cannabis orally, prepared as an infusion to drink

o Oral administration is not so popular elsewhere because the psychoactive effects are slow to begin. In the West, ingestion is often preparing cannabis in food, typically cakes or biscuits

o The effects can be unpredictable, and once swallowed there is no going back, unlink with smoking where users can choose how much to smoke depending on how intoxicated, or ‘stoned’ they being to feel, not least depending on the strength of the cannabis used

33
Q

What are the cannabinoid receptors and where are they found?
Tell me about these receptors?

A
  • CB1-mostly found in the brain
  • CB2- In peripheral tissues (especially immune system but some types of pain)
  • Receptors on cell surface coupled to G-proteins that control cAMP formation
34
Q

Tell me about the endocannabinoids structure

A

The endocannabinoids are similar in structure to endogenous fatty acids such as arachidonic acid, but the acid groups are substituted with an ethanolamine, such as anandamide

35
Q

What are the two most characterised endocannabinoids?
Whats thought to be their role?

A

The two most characterised endocannabinoids are anandamide (below) and 2-arachidonoylglycerol.

The role of endocannabinoids is still unclear but include effects on appetite and memory, analgesia, addictive behaviour

36
Q

How does THC interact with the receptors

A
  • THC binds to both CB1 and CB2 cannabinoid receptors and is a partial agonist, whereas CBD has minimal affinity for CB1 receptors. Conversely, “synthetic cannabinoids” are invariably full agonists to CB1 and CB2 receptors
  • Cannabis’ (Esp. THC) interaction with other major neurotransmitter systems (e.g., dopamine, opioid) is mainly indirect through the interplay of these systems with the endocannabinoid system
37
Q

In neuropsychopharmacology investigations, there are indications that combining doses of CBD with THC alleviates what?

A
  • In neuropsychopharmacology investigations, there are indications that combining doses of CBD with THC alleviates the initial aversive effects associated with initial administration of THC alone but will probably not alter THCs intoxicating properties.
  • It follows that cannabis used may be at an increased risk of acute adverse psychological reactions when using potent forms of cannabis with a decreased CBD content
38
Q

What is the most psychoactive ingredient of cannabis?
What effects does it cause?

A

* THC is the main psychoactive ingredient, which produced a euphoric effect or ‘high’, and merriment within the initial stages, followed by relaxation, disinhibition, and sociability

  • There are also effects on perception that accompany the ‘high’ and often contribute to it, including colours may seem brighter, music more vivid, emotions more poignant and meaningful
39
Q

What are some possible adverse effects of THC?

A
  • THC can induce psychotic symptoms, although the incidence is rare, and in contrast CBD has anxiolytic and possible anti-psychotic properties. No scientific evidence for cannabinoid “entourage” effect
40
Q

Tell me about the absorption of cannabis orally and via inhalation?

A
  • Absorption occurs immediately after first inhalation. Peak plasma levels are generally reached within 3-10 mins. Variable bioavailability (10-56%) affected by dose, history of use, individual differences in physiology, and smoking topography/ efficiency
  • with oral administration, about 90-95% is absorbed but first pass metabolism accounts for why the blood concentrations are 25-30% of those obtained by smoking
  • the onset of the effect is delayed because of slow absorption (0.5 to 2 hours), with peak plasma concentrations of THC not reached until 1 to 3 hours after ingestion
41
Q

Tell me about the distribution of cannabis

A
  • poor correlation between plasma THC levels and THC-like subjective effects. Effects continue (any may be stronger) during distribution and elimination phases
  • THC is lipophilic, binds to plasma proteins, and is quickly distributed to organs and tissues. Body fat serves as a reservoir
42
Q

What are the metabolites of cannabis?

A
  • 11-hydroxy-THC (11-OH-THC) and 11-nor-carboxy-THC (THC-COOH) are the primary metabolites of THC.

11-OH-THC is psychoactive, is equipotent to THC, and may extend duration of intoxication (important if taken orally). THC-COOH is not psychoactive

43
Q

Tell me about the elimination of cannabis

A
  • Metabolites are eliminated in the faeces (65-80%) and urine (20-35%).

Mainly THC-COOH-glucuronide in urine. Elimination half-life depends on history of use, but roughly 1.3 days for infrequent users and up to 2 weeks in heavy users.

As a considerable proportion of the metabolites are in the faeces, enterohepatic re-circulation may occur, which contributes to the long plasma half-life of THC, together with its slow release from lipophilic compartments.

44
Q

What are some effects of cannabis?

A

o Euphoria, laughter, and talkativeness
o Appetite stimulation and may promote dry mouth, dizziness and increases in visual, olfactory, and auditory perceptions (hallucinations)
o Time perception may be altered, and some users may experience anxiety and panic reactions
o Red eyes

45
Q

What can cannabis intoxication impair?

A
  • Cannabis intoxication can impair attention and shirt-term memory function (causing driving impairment) and can precipitate psychotic reactions in vulnerable individuals
  • Note: whilst often linked to cannabis, the effects of synthetic cannabinoids are very different and not just “more potent/ pronounced then cannabis”. Synthetic cannabinoid receptor agonists (SCRAs) are discussed in separate lecture
46
Q

Cannabis and driving

A
  1. Cannabis is one of the most common drugs detected in DUID cases
  2. Zero tolerance approach in UK: blood 2ng/mL limit
  3. People driving under the influence of cannabis are more likely to be involved in a car accident, but level of risk is not as great as with alcohol
  4. Some studies show that cannabis use impairs reaction time, lane control, speedometer monitoring, hand and body steadiness, breaking stop time and promotes inappropriate responses in an emergency scenario
  5. Cannabis and alcohol use combined shown to additively increase the lateral movement, but cannabis appeared to mitigate the potential for alcohol to cause increases in driving speed
47
Q

Has cannabis been linked with acute fatal overdoses?

A
  • Cannabis is not associated with acute fatal “overdoses”, this is controversial and a 2017 consensus report by the National academies of science, engineering, and medicine (NASEM) concluded that there is insufficient evidence to support or refute associations between cannabis use and increased risk of all-cause mortality and overdose lethality in humans
48
Q

What are the cardiovascular effects of cannabis?

A

Cannabis acutely increases heart rate and blood pressure but there is an uncertain association between cannabis use and heart attack

o Some limited population evidence to suggest that smoking cannabis increases the risk of ischaemic stroke

49
Q

What have several case reports of young children stated when cannabis has been accidently ingested?

A
  • Several case reports of young children accidentally ingesting cannabis and undergoing respiratory depression, tachycardia, and temporary coma.
50
Q

Other adverse effects of cannabis

A

o Regular cannabis users may experience higher rates of chronic bronchitis

o Acute cannabis use impairs certain types of cognitive function and can interfere with attention, learning and memory

o Acute cannabis intoxication precipitating a short-lasting psychotic state which reverses once the effects of the drug have abated

o Population studies have linked cannabis use to schizophrenia, with cannabis increasing the risk of developing the disorder in a dose-dependent manner, where heavier cannabis use increases the risk of developing schizophrenia, and that adolescent cannabis use may bring forward the age of schizophrenia onset but not cause it

o Some evidence for cannabis use increasing manic symptom in bipolar disorder patients; a small increased risk of developing depression; suicidal ideation, suicide attempts and completions in heavy users; and the development of social anxiety disorders.

51
Q

Other considerations with cannabis

A

o Analysis for THC, THC-COOH, 11-OH-THC and to a lesser extent, CBD, CBN is commonplace using GC-MS/MS or LC-MS-MS

o Cannabinoid concentrations often less than 100 ng/mL in blood, with THC-COOH higher than THC or 11-OH-THC

o Typically, no THC in urine; THC-COOH and 11-OH-THC present as glucuronides. Immunoassay typically analyses for THC-COOH

o Plasma/blood THC and metabolite concentrations can vary over-time (Huestis et al) and depend on many factors

o Equally, post-mortem blood THC and metabolite concentrations can also vary over-time (Chu et al) with initial reductions the increases then reductions…

o Aside from any statutory limit, virtually impossible to interpret the significance of cannabinoid concentrations in many situations (aside from indicating use at some point… but consider passive exposure)

52
Q

Therapeutic uses- “medical cannabis debate”

A
53
Q

Summary

A
  • Cannabis is one of the most widely used and abused drugs in the world. Available as plant material, resin, oils/extracts and associated products
  • Many, many phytocannabinoids exist in the plant. Delat-9-THC is the primary “active” compoenent. Cannabidiol (CBD) is also important
  • Cannabis can produce various effects, including relaxation but also impairing effects with acute toxicity concerns. Cannabinoid tox analysis is important and widespread but often difficult to interpret the results.
  • “medical cannabis” is an on-going debate focused around THC and CBD and the plant itself and associated extracts/ oils. Has approval for some therapeutic indications in some countries. Only a few defined pharmaceutical preparations at present.