6

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)

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7000 -

1943 LSD

- ,
.
19

1880
1960

1805



CD-10
F10

F11

F12

F13

F14

F15 ,

F16

F17

F18

F19



SAMHSA Household Survey on Drug Abuse, 2002

40,4%
14,4 %
3,6 %
LSD 10,4 %
9,7%
5,3%
XTC 4,3%
19,8%


45% /

72% / .




50%


(vulnerability hypothesis)

.
(self medication)


,



 -

: 12-64 .

86% 62%
.

23,7% 4,7%
.
 -

12-64

25%

14%

9,5%

1984-1993 / 5.9%- 9.5%

 .
' /
( )

, 1 9 8 4 4 5

2011 2004
3 7 .0 4 0 1 3 - 4 .7 6 9 1 2 - 6 4 ,
: , 2012 1 9 4
, : . , . , .
3. , . /
(
)
15-19


( ESPAD)

13-19
5 (20%)
7 (14%) (
)


13-14
(<2%)
17-18 4 (24,5%)
19 (51%)
1984-2011 ( 15-19 )
1984 1998
2003
2011

( ESPAD)

13-19
10 (61%)
10 (11%) 2

3 (34%)

13% 2
, , ,




( ESPAD)

:
5 17-18
(18%), 4 19 (26,8%)
4 17-18 (22,7%)
3 19 (32,8%)
1984-2011 ( 15-19 )
,

2007-2011


4


( ESPAD)

15-19
7 (15,2%) (
) , .
.

( ~ 2,5 1)



( ESPAD)

: 17-18
7 (13,6%)
8%

13-14 2,6% 0,9%

1984-2011 ( 15-19 )

( 6% 1984 15,3% 2011)

( 3+ )



(-) (Hopfer et al 2003)
50-60%
(Kendler 1999)

40% (Tsuang
et al 1996), (Kendler et al 1999) 60-
70%
 Addictions Array HPA & Adrenergic
130 Genes
Tagged with Stress Other Metabolic Serotonin
ADRA1A BDNF ALDH1A
1350 SNPs CRH ADRA2A CCK ALDH2 HTR1A
CRHBP CAT HTR1B
CRHR1
ADRA2B
ADRA2C
CCKAR
CYP2E1 Dopamine HTR2A
CCKBR
CRHR2 ADRB2 ADH1A HTR2C
CLOCK DDC
GAL ARRB2 ADH1B HTR3A
HCRT DRD1
NPY SLC6A2 ADH1C HTR3B
OXT DRD2
NPY1R DBH ADH4 MAOA
NR3C1 DRD3
NPY2R MAOB
Signal NPY5R
SLC29A1 ADH5
ADH6
DRD4
SLC6A3
TAC1 DRD5
Transduction CART ADH7 SLC18A2 SLC6A4
TPH2
TH
ADCY7
AVPR1A Cholinergic COMT
AVPR1B
CDK5R1 CHRM1
CREB1 CHRM2 GABA
CSNK1E CHRM3
FEV CHRM4 GABRA2
FOS CHRM5 GABRA4
FOSL1 CHRNA4 GABRA6
FOSL2 CHRNB2 GABRB1
GSK3B GABRB2
JUN GABRB3
MAPK1 GABRD
MAPK3 GABRG2
MPDZ Opioid GABRG3
NGFB OPRM1 SLC6A11
NTRK2
NTSR1
NMDA Glycine OPRD1 SLCSA13
GAD1
OPRK1
NTSR2 Cannabinoid GRIK1 OPRL1 GAD2
PPP1R1 GRIN1 GLRA1 PDYN VIAAT
BPRKCE GRIN2A GLRA2 PENK DBI
CNR1 GRIN2B
FAAH GLRB PNOC
GRM1 GPHN POMC
: D. Goldman, NIH




, ,

,

,



(nucleous accumbens)
H
(
)
(nucleous accumbens)
D3
(learning associations)

, ,
,
 ) Binge/intoxication stage. Reinforcing effects of drugs may
engage reward neurotransmitters and associative mechanisms in
the nucleus accumbens shell and core and then engage
stimulusresponse habits that depend on the dorsal striatum. Two
major neurotransmitters mediating the rewarding effects of drugs
of abuse are dopamine and opioid peptides.

(b) Withdrawal/negative affect stage.

The negative emotional state of withdrawal may engage the
activation of the extended amygdala. The extended amygdala is
composed of several basal forebrain structures, including the bed
nucleus of the stria terminalis, central nucleus of the amygdala,
and possibly a transition zone in the medial portion (or shell) of
the nucleus accumbens. Major neurotransmitters in the extended
amygdala hypothesized to have a function in negative
reinforcement are corticotropin-releasing factor, norepinephrine,
and dynorphin. Major projections of the extended amygdala are
to the hypothalamus and brainstem.

(c) Preoccupation/anticipation (craving) stage. This stage involves

the processing of conditioned reinforcement in the BLA and the
processing of contextual information by the hippocampus.
Executive control depends on the prefrontal cortex and includes
representation of contingencies, representation of outcomes, and
their value and subjective states (ie, craving and, presumably,
feelings) associated with drugs. The subjective effects termed
drug craving in humans involve activation in functional imaging
studies of the orbital and anterior cingulate cortices and temporal
lobe, including the amygdala. A major neurotransmitter involved
in the craving stage is glutamate localized in pathways from
frontal regions and the BLA that project to the ventral striatum

Neu r al c ir c uit r y a s s o c ia t ed w it h t h e
t h r ee s t ages o f t h e a ddic t io n c yc l e

Koob & Volkow 2010, Neurocircuitry of Addiction



-

50%












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1984 4300
25% 18-64
12.8% 12-17


(Ciraulo
et al 2003)



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