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1
Endocannabinoids, cannabinoids and cannabis
Celia Morgan
University of Exeter
2
Cannabis
3
Cannabis
4
Cannabis
5
Cannabis
• Trichomes on cannabis
plant • Evolved to protect the
plant • Contain chemicals:
‘cannabinoids’
6
Cannabinoids > 80 different cannabinoids Δ9-tetrahydrocannabinol
(THC) induces anxiety, memory impairment, ‘stoned’ and schizophrenia-like effects (D’Souza et al, 2004; 2008).
Cannabidiol (CBD) anxiolytic, reduces paranoia, neuroprotective (Zuardi et al. 2006; Hermann et al. 2007; Leweke et al, 2007).
7
• Different types of cannabis vary in levels of cannabinoids
Afghani - BC bud – big bud – bomb – Blue velvet – boo-yah – bubble – bud – buddha – burger – Charis – chiba – chino – choke – cigga-weed – cigweed – combustible herbage – crippy – dank - dirt weed – ditch weed – doja – doob – dope – drat – draw – dro – dub – dube – Dutchie – endo – erve – gange – ganja – giggle stick – gonj – grass – green – green bud – hash - heim – herb – herbal refreshment – Holland’s Hope – hog leg – hooter – hydro – indica – indo – jib –– keef – kief – Kush – Mary Jane – Mexican dirt weed – MJ – Mr. J – Nepalese - Northern Lights – paca lolo – Purple Haze – pot – purp –– Lebanese red - reggie – schwag –silver weed – skunk – smoke – soapbar tea – Thai stick – treats – tweed – wacky baccy – vortex - weed – White Widow - woolies – zombie
http://images.google.co.uk/imgres?imgurl=http://a.abcnews.com/images/Health/apg_marijuana_070727_ms.jpg&imgrefurl=http://abcnews.go.com/Health/CancerPreventionAndTreatment/wireStory?id=4207595&h=310&w=413&sz=18&hl=en&start=45&tbnid=1jTDEG1rK3BSLM:&tbnh=94&tbnw=125&prev=/images?q=cannabis&start=36&gbv=2&ndsp=18&hl=en&sa=N
8
Levels of THC and CBD in 3000 cannabis seizures UK
King and Hardwick, 2008
9
Increasing THC potency in UK cannabis seizures
12.13
2011
10
Cannabis samples collected, n=422
Chart2
skunk
herbal
resin / hashish
70
10
13
Sheet1
skunkherbalresin / hashish
Recreational users4137
Daily users2976
Group * skunk herbal hash Crosstabulation
skunk herbal hashTotal
skunkherbalresin / hashish
Grouprecreational userCount413751skunkherbalresin / hashish
% within Group80.39215686275.882352941213.7254901961100701013
% within skunk herbal hash58.57142857143053.846153846254.8387096774
% of Total44.08602150543.22580645167.526881720454.8387096774
daily userCount297642
% within Group69.047619047616.666666666714.2857142857100
% within skunk herbal hash41.42857142867046.153846153845.1612903226
% of Total31.18279569897.52688172046.451612903245.1612903226
TotalCount70101393
% within Group75.268817204310.75268817213.9784946237100
% within skunk herbal hash100100100100
% of Total75.268817204310.75268817213.9784946237100
Sheet1
Sheet2
Sheet3
11
n = 371
CBD and THC levels
12
n = 371 CBD levels
are declining: why?
CBD and THC levels
13
Preferences for types of cannabis in 16-23 year olds
Chart1
no preference
Resin/ hash
Low potency herbal
Skunk
28
21
26
39
Sheet1
Do you have a preference for a type of cannabis
Frequency
Validno preference28
Resin/ hash21
Low potency herbal26
Skunk39
Sheet1
Sheet2
Sheet3
14
Where has the CBD gone?
• Potter (2010) • Majority of UK consumed
cannabis now grown intensively in illegal ‘farms’
• Intensive heating decreases levels of CBD in trichomes
• Hashish combines a variety of cannabis plants – Most cannabis seeds in UK
now are a variety with no CBD
15
Skunk and cannabis use disorder • Cannabis second only to heroin as reason for presentation at drug services
across EU – 25% cases (EMCDDA, 2014)
16
‘Skunk’ use linked to psychosis
Di Forti et al., 2015, Lancet Psychiatry
17
Research question • Given that levels of cannabinoids vary in different cannabis
preparations • THC and CBD have opposing effects in the laboratory • Skunk use is more prevalent in psychosis and cannabis use
disorder
18
Research question • Given that levels of cannabinoids vary in different cannabis
preparations • THC and CBD have opposing effects in the laboratory • Skunk use is more prevalent in psychosis and cannabis use
disorder Does CBD protect against the harmful effects of THC in cannabis users?
19
• Study 1: Cannabinoids in hair • Study 2: Naturally occurring cannabinoids in
hair and cannabis
20
Looking at cannabinoids in the hair…
21
Looking at cannabinoids in the hair…
~ 3 years
22
Study 1: THC/CBD in hair
• Hair analysis • 3cm hair samples ~ 3 months • 132 people, mean age 27 years
23
Psychotic-like experiences: O-LIFE – Unusual Experiences ~ Paranoia, Illusions & Delusions
• When you look in the mirror does your face sometimes seem quite different from usual?
• Do think you could learn to read others minds if you wanted to? • Do you sometimes think people are laughing about you behind your
back?
THC only n=20
CBD and THC n=26
Neither n=86
Study 1: THC/CBD in hair
24
**
Study 1: THC/CBD in hair
THC/CBD in hair
Morgan & Curran, 2008 British Journal of Psychiatry
Chart1
Unusual ExperiencesUnusual ExperiencesUnusual Experiences
No Cannabis
THC only
THC + CBD
OLIFE Score
3.5
6.8
4.05
Sheet1
Unusual ExperiencesCognitive DisorganisationIntrovertive AnhedoniaImpulsive Non-conformity0.50.30.20.2
No Cannabis3.54.95.55.20.750.40.40.4
THC only6.85.35.35.350.50.50.30.3
THC + CBD4.055.14.35.3
Sheet1
0.50.750.5
0.30.40.5
0.20.40.3
0.20.40.3
No Cannabis
THC only
THC + CBD
Sheet2
Sheet3
25
THC / CBD
• Cannabis users with THC only in hair experience higher levels of unusual experiences than THC+CBD
Interpretations:
- Pre-existing group differences? - Is CBD protective against psychotic-like effects of THC?
Study 1: THC/CBD in hair
26
Study 2: Naturalistic study of the effects of cannabinoids
• n=626 individuals; 16-23 year olds • Tested in own home, smoking own supply of cannabis • Tested cannabis smoked for CBD and THC • Looked at hair for chronic use
Sober
Stoned
Stoned
Sober Day 0
Day 7
27
*
Same amount of THC; differed in CBD
Acute effects: memory
Morgan et al. (2010) British Journal of Psychiatry
Study 2: Naturalistic study of cannabinoids
Chart1
IntoxicatedIntoxicated
Not intoxicatedNot intoxicated
Low CBD:THC
High CBD:THC
Delayed prose recall
4.7813
6.8103
6.25
6.569
Verbal fluency
IntoxicatedNot intoxicated
Low CBD:THC16.062513.8125
High CBD:THC16.103416.6207
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC1.00996768660.9195870656
High CBD:THC0.83540061650.8226097992
Verbal fluency
1.00996768660.8354006165
0.91958706560.8226097992
Low CBD:THC
High CBD:THC
Verbal fluency
Category fluency
IntoxicatedNot intoxicated
Low CBD:THC16.718816.75
High CBD:THC19.620718.4138
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.65259238390.8364189338
High CBD:THC0.92103773560.8545978006
Category fluency
0.65259238390.9210377356
0.83641893380.8545978006
Low CBD:THC
High CBD:THC
Category fluency
Prose delayed
IntoxicatedNot intoxicated
Low CBD:THC4.78136.25
High CBD:THC6.81036.569
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.50097631560.7010221273
High CBD:THC0.72491374730.5849737404
Prose delayed
0.50097631560.7249137473
0.70102212730.5849737404
Low CBD:THC
High CBD:THC
Prose delayed
PSI
IntoxicatedNot intoxicated
Low CBD:THC26.387116.4194
High CBD:THC29.545518.7727
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC2.7861703531.5792837891
High CBD:THC3.7107115643.5547253919
PSI
2.7861703533.710711564
1.57928378913.5547253919
Low CBD:THC
High CBD:THC
PSI
Stoned rating
IntoxicatedNot Intoxicated
Low CBD:THC6.6251.3438
High CBD:THC6.44831.3448
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.24842075440.3528392127
High CBD:THC0.20022042750.359892421
Stoned rating
0.24842075440.2002204275
0.35283921270.359892421
Low CBD:THC
High CBD:THC
Stoned data (cm)
line graph
FoodNeutralDrug
Low CBD:THC0.95410.14030.9081
High CBD:THC0.6950.03080.265
SE-FoodSE- NeutralSE -Drug
Low CBD:THC0.09256857270.12773349470.0939605138
High CBD:THC0.12986136690.10211009070.1498495888
line graph
0.09256857270.09256857270.12986136690.1298613669
0.12773349470.12773349470.10211009070.1021100907
0.09396051380.09396051380.14984958880.1498495888
Low CBD:THC
High CBD:THC
Pleasantness Rating
28
*
Same amount of THC; differed in CBD
Acute effects: memory
Morgan et al. (2010) British Journal of Psychiatry
Chart1
IntoxicatedIntoxicated
Not intoxicatedNot intoxicated
Low CBD:THC
High CBD:THC
Delayed prose recall
4.7813
6.8103
6.25
6.569
Verbal fluency
IntoxicatedNot intoxicated
Low CBD:THC16.062513.8125
High CBD:THC16.103416.6207
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC1.00996768660.9195870656
High CBD:THC0.83540061650.8226097992
Verbal fluency
1.00996768660.8354006165
0.91958706560.8226097992
Low CBD:THC
High CBD:THC
Verbal fluency
Category fluency
IntoxicatedNot intoxicated
Low CBD:THC16.718816.75
High CBD:THC19.620718.4138
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.65259238390.8364189338
High CBD:THC0.92103773560.8545978006
Category fluency
0.65259238390.9210377356
0.83641893380.8545978006
Low CBD:THC
High CBD:THC
Category fluency
Prose delayed
IntoxicatedNot intoxicated
Low CBD:THC4.78136.25
High CBD:THC6.81036.569
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.50097631560.7010221273
High CBD:THC0.72491374730.5849737404
Prose delayed
0.50097631560.7249137473
0.70102212730.5849737404
Low CBD:THC
High CBD:THC
Prose delayed
PSI
IntoxicatedNot intoxicated
Low CBD:THC26.387116.4194
High CBD:THC29.545518.7727
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC2.7861703531.5792837891
High CBD:THC3.7107115643.5547253919
PSI
2.7861703533.710711564
1.57928378913.5547253919
Low CBD:THC
High CBD:THC
PSI
Stoned rating
IntoxicatedNot Intoxicated
Low CBD:THC6.6251.3438
High CBD:THC6.44831.3448
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.24842075440.3528392127
High CBD:THC0.20022042750.359892421
Stoned rating
0.24842075440.2002204275
0.35283921270.359892421
Low CBD:THC
High CBD:THC
Stoned data (cm)
line graph
FoodNeutralDrug
Low CBD:THC0.95410.14030.9081
High CBD:THC0.6950.03080.265
SE-FoodSE- NeutralSE -Drug
Low CBD:THC0.09256857270.12773349470.0939605138
High CBD:THC0.12986136690.10211009070.1498495888
line graph
0.09256857270.09256857270.12986136690.1298613669
0.12773349470.12773349470.10211009070.1021100907
0.09396051380.09396051380.14984958880.1498495888
Low CBD:THC
High CBD:THC
Pleasantness Rating
29
Attentional Bias
• Cues associated with drug use (e.g. cannabis, pipe, joint) grab the users’ attention
• Increases drug craving and predicts relapse
30
* *
31
* *
32
Exposure: 250ms or 2000ms
33
* *
34
35
* *
36
37
-60-40-20
020406080
100120
Food Drug
Not Intoxicated
Atte
ntio
nal b
ias
(ms)
Low CBD:THCHigh CBD:THC
Stimulus exposure = 250ms Morgan, Freeman, Schafer & Curran (2010)
Neuropsychopharmacology
Dependence Attentional Bias Study 2: Naturalistic study of cannabinoids
Chart1
13.940997281418.7402758438
18.643240227115.4756500478
Food Not IntoxicatedFood Not Intoxicated17.790069469718.3150511554
DrugDrug10.915995321710.5135063612
Low CBD:THC
High CBD:THC
Attentional bias (ms)
-0.5267383226
12.595
83.0123655806
88.1788386333
Verbal fluency
IntoxicatedNot intoxicated
Low CBD:THC16.062513.8125
High CBD:THC16.103416.6207
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC1.00996768660.9195870656
High CBD:THC0.83540061650.8226097992
Verbal fluency
1.00996768660.8354006165
0.91958706560.8226097992
Low CBD:THC
High CBD:THC
Verbal fluency
Category fluency
IntoxicatedNot intoxicated
Low CBD:THC16.718816.75
High CBD:THC19.620718.4138
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.65259238390.8364189338
High CBD:THC0.92103773560.8545978006
Category fluency
0.65259238390.9210377356
0.83641893380.8545978006
Low CBD:THC
High CBD:THC
Category fluency
Not intoxicated only_prose dela
Not intoxicated
Low CBD:THC6.25
High CBD:THC6.569
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.50097631560.7010221273
High CBD:THC0.72491374730.5849737404
Not intoxicated only_prose dela
0.70102212730.5849737404
Low CBD:THC
High CBD:THC
Prose delayed
Prose delayed
IntoxicatedNot intoxicated
Low CBD:THC4.78136.25
High CBD:THC6.81036.569
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.50097631560.7010221273
High CBD:THC0.72491374730.5849737404
Prose delayed
0.50097631560.7249137473
0.70102212730.5849737404
Low CBD:THC
High CBD:THC
Prose delayed
PSI
IntoxicatedNot intoxicated
Low CBD:THC26.387116.4194
High CBD:THC29.545518.7727
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC2.7861703531.5792837891
High CBD:THC3.7107115643.5547253919
PSI
2.7861703533.710711564
1.57928378913.5547253919
Low CBD:THC
High CBD:THC
PSI
Stoned rating
IntoxicatedNot Intoxicated
Low CBD:THC6.6251.3438
High CBD:THC6.44831.3448
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.24842075440.3528392127
High CBD:THC0.20022042750.359892421
Stoned rating
0.24842075440.2002204275
0.35283921270.359892421
Low CBD:THC
High CBD:THC
Stoned data (cm)
line graph
FoodNeutralDrug
Low CBD:THC0.95410.14030.9081
High CBD:THC0.6950.03080.265
SE-FoodSE- NeutralSE -Drug
Low CBD:THC0.09256857270.12773349470.0939605138
High CBD:THC0.12986136690.10211009070.1498495888
line graph
0.09256857270.09256857270.12986136690.1298613669
0.12773349470.12773349470.10211009070.1021100907
0.09396051380.09396051380.14984958880.1498495888
Low CBD:THC
High CBD:THC
Rating
attentional bias not intoxicatd
Mean
Descriptives
Not IntoxicatedStd. Error
FoodDrug
Low CBD:THC-0.526738322683.012365580613.940997281418.643240227117.790069469710.9159953217
High CBD:THC12.59588.178838633318.740275843815.475650047818.315051155410.5135063612
Drug_intoxicated1
2
Drug Non_intoxicated1
2
Food Non-intoxicated1
2
attentional bias not intoxicatd
13.940997281418.7402758438
18.643240227115.4756500478
17.790069469718.3150511554
10.915995321710.5135063612
Low CBD:THC
High CBD:THC
Bias (ms)
Attentional bias both
IntoxicatedNot IntoxicatedStd. Error
FoodDrugFoodDrug
Low CBD:THC40.139652812529.0633804688-0.526738322683.012365580613.940997281418.643240227117.790069469710.9159953217
High CBD:THC-9.080355875-45.773671843812.59588.178838633318.740275843815.475650047818.315051155410.5135063612
Attentional bias both
13.940997281418.7402758438
18.643240227115.4756500478
17.790069469718.3150511554
10.915995321710.5135063612
Low CBD:THC
High CBD:THC
Bias (ms)
38
-60-40-20
020406080
100120
Food Drug Food Drug
Intoxicated Not Intoxicated
Atte
ntio
nal B
ias
(ms)
Low CBD:THCHigh CBD:THC
Morgan, Freeman, Schafer & Curran (2010) Neuropsychopharmacology
* *
Dependence Attentional Bias
Study 2: Naturalistic study of cannabinoids
Chart2
Food IntoxicatedFood Intoxicated13.940997281418.7402758438
DrugDrug18.643240227115.4756500478
Food Not IntoxicatedFood Not Intoxicated17.790069469718.3150511554
DrugDrug10.915995321710.5135063612
Low CBD:THC
High CBD:THC
Attentional Bias (ms)
40.1396528125
-9.080355875
29.0633804688
-45.7736718438
-0.5267383226
12.595
83.0123655806
88.1788386333
Verbal fluency
IntoxicatedNot intoxicated
Low CBD:THC16.062513.8125
High CBD:THC16.103416.6207
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC1.00996768660.9195870656
High CBD:THC0.83540061650.8226097992
Verbal fluency
1.00996768660.8354006165
0.91958706560.8226097992
Low CBD:THC
High CBD:THC
Verbal fluency
Category fluency
IntoxicatedNot intoxicated
Low CBD:THC16.718816.75
High CBD:THC19.620718.4138
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.65259238390.8364189338
High CBD:THC0.92103773560.8545978006
Category fluency
0.65259238390.9210377356
0.83641893380.8545978006
Low CBD:THC
High CBD:THC
Category fluency
Not intoxicated only_prose dela
Not intoxicated
Low CBD:THC6.25
High CBD:THC6.569
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.50097631560.7010221273
High CBD:THC0.72491374730.5849737404
Not intoxicated only_prose dela
0.70102212730.5849737404
Low CBD:THC
High CBD:THC
Prose delayed
Prose delayed
IntoxicatedNot intoxicated
Low CBD:THC4.78136.25
High CBD:THC6.81036.569
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.50097631560.7010221273
High CBD:THC0.72491374730.5849737404
Prose delayed
0.50097631560.7249137473
0.70102212730.5849737404
Low CBD:THC
High CBD:THC
Prose delayed
PSI
IntoxicatedNot intoxicated
Low CBD:THC26.387116.4194
High CBD:THC29.545518.7727
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC2.7861703531.5792837891
High CBD:THC3.7107115643.5547253919
PSI
2.7861703533.710711564
1.57928378913.5547253919
Low CBD:THC
High CBD:THC
PSI
Stoned rating
IntoxicatedNot Intoxicated
Low CBD:THC6.6251.3438
High CBD:THC6.44831.3448
Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency
Low CBD:THC0.24842075440.3528392127
High CBD:THC0.20022042750.359892421
Stoned rating
0.24842075440.2002204275
0.35283921270.359892421
Low CBD:THC
High CBD:THC
Stoned data (cm)
line graph
FoodNeutralDrug
Low CBD:THC0.95410.14030.9081
High CBD:THC0.6950.03080.265
SE-FoodSE- NeutralSE -Drug
Low CBD:THC0.09256857270.12773349470.0939605138
High CBD:THC0.12986136690.10211009070.1498495888
line graph
0.09256857270.09256857270.12986136690.1298613669
0.12773349470.12773349470.10211009070.1021100907
0.09396051380.09396051380.14984958880.1498495888
Low CBD:THC
High CBD:THC
Rating
attentional bias
Mean
Descriptives
IntoxicatedNot IntoxicatedStd. Error
FoodDrugFoodDrug
Low CBD:THC40.139652812529.0633804688-0.526738322683.012365580613.940997281418.643240227117.790069469710.9159953217
High CBD:THC-9.080355875-45.773671843812.59588.178838633318.740275843815.475650047818.315051155410.5135063612
Drug_intoxicated1
2
Drug Non_intoxicated1
2
Food Non-intoxicated1
2
attentional bias
13.940997281418.7402758438
18.643240227115.4756500478
17.790069469718.3150511554
10.915995321710.5135063612
Low CBD:THC
High CBD:THC
Bias (ms)
39
Paranoia and ‘stoned’ effects
• Levels of CBD in cannabis smoked did not impact on acute psychotic like effects of cannabis
• No difference in ‘stoned’ ratings between high and low CBD groups
Study 2: Naturalistic study of cannabinoids
Morgan et al. (2011) Psychological Medicine
40
Acute effects of cannabinoids
• Acutely CBD protects from memory impairment of THC
• Greater attentional bias in people smoking low CBD cannabis
Study 2: Naturalistic study – Chronic effects Study 2: Naturalistic study of cannabinoids
41
Chronic effects of cannabinoids on psychotic symptoms
• Looked at CBD and THC in hair • Replicated previous findings Morgan & Curran (2008) • Psychotic symptoms higher in those smoking
cannabis with no CBD – Highest in infrequent users smoking high THC
cannabis with no CBD
Study 2: Naturalistic study – Chronic effects Study 2: Naturalistic study of cannabinoids
42
Acute effects of cannabinoids in cannabis smokers: laboratory study
PLACEBO 16mg CBD
8mg THC 8mg THC +16 mg CBD
• 48 participants • Selected to be:
• 24 daily users • 24 less frequent
• Of those • 50% High psychosis
proneness / schizotypy : (top quartile)
• 50% Low psychosis proneness / schizotypy (bottom quartile)
43
Acute effects of cannabinoids in cannabis smokers: laboratory study
• Inhaled CBD and THC through a ‘Volcano’
• Aimed to reverse the acute psychotic effects of THC in line with laboratory studies (Bhattarcharya et al., 2010)
44
• Psychotic symptoms greater following THC
Study 3: Acute effects of CBD/THC in laboratory
45
CBD reduces THC induced psychotic symptoms?
5
10
15
20
25
30
35
40
THC THC + CBD CBD Placebo
PSI
SC
OR
E
Low schizotypy, recreational
High schizotypy, recreational
Low schizotypy, daily
High schizotypy, daily
Study 3: Acute effects of CBD/THC in laboratory
46
CBD and memory in the laboratory
47
CBD and memory
• Measure startle response from electrical impulses in skin
48
CBD in the laboratory
49
CBD in the laboratory
• CBD speeds up ‘forgetting’ of associations… ‘extinction learning’
• Forgetting has important therapeutic implications in treatment of psychiatric disorders…
• Phobias – e.g. spider with fear response • Substance use – e.g. drugs with pleasure
50
CBD to reduce cigarette smoking?
• n=24 smokers not actively quitting
• Half given CBD inhaler, half placebo
• Ad hoc use over a week
• 40% reduction in cigarette smoking in CBD group
0
20
40
60
80
100
120
Pre Post Follow-up
Num
ber
of c
igar
ette
s sm
oked
per
w
eek Placebo
CBD
**
n
Morgan et al., 2013 Addictive Behaviour
51
Use of CBD in therapy
52
How does cannabis act on the brain?
53
How does cannabis act on the brain?
Raphael Mechoulam Asked Israeli police to give him 5kg cannabis. He discovered THC and later CBD.
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=426vnPZBmdEiYM&tbnid=QNJFlYs4jKID3M:&ved=0CAUQjRw&url=http://www.cannabisterapeutica.info/tag/farmaco/&ei=wVgHU_O4MYGw0QXk4IHgDw&bvm=bv.61725948,d.ZG4&psig=AFQjCNElvRF4iySoZt7j9NDfDK-IgOpxlw&ust=1393076656373952
54
How does cannabis act on the brain?
Raphael Mechoulam Asked Israeli police to give him 5kg cannabis. He discovered THC and later CBD. Howlett, discovered cannabinoid receptors – CB1 in brain; CB2 immune system.
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=426vnPZBmdEiYM&tbnid=QNJFlYs4jKID3M:&ved=0CAUQjRw&url=http://www.cannabisterapeutica.info/tag/farmaco/&ei=wVgHU_O4MYGw0QXk4IHgDw&bvm=bv.61725948,d.ZG4&psig=AFQjCNElvRF4iySoZt7j9NDfDK-IgOpxlw&ust=1393076656373952
55
How does cannabis act on the brain?
Raphael Mechoulam Asked Israeli police to give him 5kg cannabis. He discovered THC and later CBD. Howlett, discovered cannabinoid receptors – CB1 in brain; CB2 immune system.
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=426vnPZBmdEiYM&tbnid=QNJFlYs4jKID3M:&ved=0CAUQjRw&url=http://www.cannabisterapeutica.info/tag/farmaco/&ei=wVgHU_O4MYGw0QXk4IHgDw&bvm=bv.61725948,d.ZG4&psig=AFQjCNElvRF4iySoZt7j9NDfDK-IgOpxlw&ust=1393076656373952
56
How does cannabis act on the brain?
Raphael Mechoulam Asked Israeli police to give him 5kg cannabis. He discovered THC and later CBD. Howlett, discovered cannabinoid receptors – CB1 in brain; CB2 immune system. Raphael’s team discovered the ‘brain’s own cannabis’ - anandamide (ananda = bliss/ delight in Sanscrit) & 2-AG. .
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=426vnPZBmdEiYM&tbnid=QNJFlYs4jKID3M:&ved=0CAUQjRw&url=http://www.cannabisterapeutica.info/tag/farmaco/&ei=wVgHU_O4MYGw0QXk4IHgDw&bvm=bv.61725948,d.ZG4&psig=AFQjCNElvRF4iySoZt7j9NDfDK-IgOpxlw&ust=1393076656373952
57
Endocannabinoids Phytocannabinoids Synthetic cannabinoids brain plant manufactured
CB1 & CB2 receptors Pleasure, addiction, pain, appetite, memory,
immune system, mental health
http://www.easyvectors.com/assets/images/vectors/afbig/chemistry-lab-flask-clip-art.jpg
58
Endocannabinoids in psychosis • AEA increased in antipsychotic-
naïve first-episode psychosis (Leweke et al., 1999, Guiffrida et al. 2004)
• Drops off in chronic schiz • Modulate excessive DA release? • Downregulation of
endocannabinoid signalling following repeated THC administration in rats (DiMarzo et al., 2000)
59
Looking at endocannabinoids in cannabis users
• AEA in blood does not correlate with
brain • Collected CSF from lumbar punctures • 21 cannabis users (mean age
22.0±2.91) • 13 matched controls (mean age
22.1±2.45 ) • PSI to assess psychotic symptoms
60
AEA in cannabis users
0.05
0.07
0.09
0.11
0.13
0.15
0.17
0.19
Control Low Heavy
AE
A, p
mol
/mol
Morgan et al., 2013 Brit J Psych
r= -0.536, p=0.02
61
Endocannabinoids and psychosis
• Lower AEA in heavy users • Chronic downregulation of anandamide through repeated
THC administration • How cannabis increases risk of psychosis?
• Negative correlation with symptom severity – Consistent with findings in psychosis
62
Endocannabinoids and Cannabinoids
• CBD may block the reuptake and hydrolysis of anandamide
• CBD increases levels of AEA in patients with schizophrenia
• CBD improves psychotic symptoms in patients with schizophrenia (Leweke et al., 2012 Translational Psych)
63
Conclusions
THC Induces anxiety Psychotic-like
effects. Impairs
memory and learning
CBD Reduces anxiety Anti-psychotic
effects Enhances learning
and blocks THC memory loss
http://www.texample.net/media/tikz/examples/PDF/yin-and-yang.pdf
64
Conclusions
• CBD is emerging as an important medicine • CBD levels are declining in street cannabis
– Alongside increasing levels of THC may increase the harms of the drug
• Smoking hash / resin (if available) reduce the harm
65
What implications does our scientific understanding of cannabis have for
debates about legalisation?
• Taking control of the cannabis market could allow rich CBD forms of cannabis to become widely available.
• This could help protect young people from the mental health harms of high THC/skunk forms.
66
Medical Marijuana: US
www.leafly.com
http://www.leafly.com
67
Medical Marijuana US
www.leafly.com
http://www.leafly.com
68
Medical Marijuana: US
www.leafly.com
http://www.leafly.com
69
Acknowledgements
UCL Val Curran Tom Freeman Grainne Schafer Chelsea Gardner Emma Page Centre for Anaesthesia Brigitta Brandner Kate Chatten Sumit Galati Amod Manocha IoP John Powell CIMH Mannheim Markus Leweke Christina Schaefer
70
Thanks!
Endocannabinoids, cannabinoids and cannabisCannabisCannabisCannabisCannabisCannabinoidsSlide Number 7Levels of THC and CBD in 3000 cannabis seizures UKIncreasing THC potency in UK cannabis seizuresCannabis samples collected, n=422CBD and THC levels CBD and THC levels Preferences for types of cannabis in 16-23 year oldsSlide Number 14Slide Number 15‘Skunk’ use linked to psychosisResearch questionResearch questionSlide Number 19Looking at cannabinoids in the hair…Looking at cannabinoids in the hair…Study 1: THC/CBD in hair Slide Number 23THC/CBD in hairTHC / CBDStudy 2: Naturalistic study of the effects of cannabinoids��Slide Number 27Slide Number 28Slide Number 29Slide Number 30Slide Number 31Slide Number 32Slide Number 33Slide Number 34Slide Number 35Slide Number 36Slide Number 37Slide Number 38Paranoia and ‘stoned’ effectsAcute effects of cannabinoidsChronic effects of cannabinoids on psychotic symptomsAcute effects of cannabinoids in cannabis smokers: laboratory studyAcute effects of cannabinoids in cannabis smokers: laboratory studySlide Number 44CBD reduces THC induced psychotic symptoms?CBD and memory in the laboratoryCBD and memoryCBD in the laboratoryCBD in the laboratoryCBD to reduce cigarette smoking?Use of CBD in therapy How does cannabis act on the brain?How does cannabis act on the brain?How does cannabis act on the brain?How does cannabis act on the brain?How does cannabis act on the brain?Slide Number 57Endocannabinoids in psychosisLooking at endocannabinoids in cannabis usersAEA in cannabis usersEndocannabinoids and psychosisEndocannabinoids and CannabinoidsConclusionsConclusions��What implications does our scientific understanding of cannabis have for debates about legalisation? �Medical Marijuana: USMedical Marijuana USMedical Marijuana: USSlide Number 69Slide Number 70