Background: Hypophosphatasia (HPP) is a rare congenital disease caused by a mutation affecting tissue nonspecific alkaline phosphatase, an enzyme involved in phosphate metabolism. The clinical manifestation usually includes bone mineralization disorders, neurological symptoms, and persistent muscle pain. Case Report: This case involves a woman in her sixties of Central European descent who suffers from lifelong chronic pain and muscle weakness due to HPP and concomitant degenerative changes of the lumbar spine. The patient is physically impaired and limited in her ability to walk as a result. HPP-specific and guideline-based multimodal pain management including enzyme replacement therapy with asfotase alfa, opioids, invasive orthopedic and neurosurgical procedures, long-term physiotherapy, and psychotherapy did not yield sufficient treatment results. The average pain was given as 8.5 on a numerical rating scale (NRS, 0–10) for the last 3 years. Treatment with a cannabidiol-predominant, full-spectrum, prescription cannabis extract led to a clinically meaningful pain reduction to 2.5/10 NRS, a discontinuation of opioids, and a recent resumption of employment as a physician. Conclusion: A more widespread consideration of medical cannabinoids in the treatment of complex chronic pain is proposed. Cannabinoids may pose a particularly potent treatment option for HPP-related symptoms and inflammation due to their known anti-inflammatory properties.

1.
Mornet
E
.
Hypophosphatasia
.
Best Pract Res Clin Rheumatol
.
2008
;
22
(
1
):
113
27
.
2.
Linglart
A
,
Biosse-Duplan
M
.
Hypophosphatasia
.
Curr Osteoporos Rep
.
2016
;
14
(
3
):
95
105
.
3.
Whyte
MP
.
Hypophosphatasia
.
Pediatric Bone Elsevier
;
2012
. p.
771
94
.
4.
Chodirker
BN
,
Coburn
SP
,
Seargeant
LE
,
Whyte
MP
,
Greenberg
CR
.
Increased plasma pyridoxal-5′-phosphate levels before and after pyridoxine loading in carriers of perinatal/infantile hypophosphatasia
.
J Inherit Metab Dis
.
1990
;
13
(
6
):
891
6
.
5.
Girschick
HJ
,
Schneider
P
,
Haubitz
I
,
Hiort
O
,
Collmann
H
,
Beer
M
,
.
Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia
.
Orphanet J Rare Dis
.
2006
;
1
(
1
):
24
12
.
6.
Moss
KE
.
140 Six cases of hypophosphatasia presenting with musculoskeletal symptoms diagnosed in a general rheumatology clinic
.
Rheumatology
.
2019
;
58
(
Suppl 3
):
kez108048
.
7.
Waymire
KG
,
Mahuren
JD
,
Jaje
JM
,
Guilarte
TR
,
Coburn
SP
,
MacGregor
GR
.
Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6
.
Nat Genet
.
1995
;
11
(
1
):
45
51
.
8.
Mornet
E
,
Yvard
A
,
Taillandier
A
,
Fauvert
D
,
Simon-Bouy
B
.
A molecular-based estimation of the prevalence of hypophosphatasia in the European population
.
Ann Hum Genet
.
2011
;
75
(
3
):
439
45
.
9.
Lia-Baldini
AS
,
Muller
F
,
Taillandier
A
,
Gibrat
JF
,
Mouchard
M
,
Robin
B
,
.
A molecular approach to dominance in hypophosphatasia
.
Hum Genet
.
2001
;
109
(
1
):
99
108
.
10.
Herasse
M
,
Spentchian
M
,
Taillandier
A
,
Keppler-Noreuil
K
,
Fliorito
AN
,
Bergoffen
J
,
.
Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase gene
.
J Med Genet
.
2003
;
40
(
8
):
605
9
.
11.
Fraser
D
.
Hypophosphatasia
.
Am J Med
.
1957
;
22
(
5
):
730
46
.
12.
Watanabe
A
,
Karasugi
T
,
Sawai
H
,
Naing
BT
,
Ikegawa
S
,
Orimo
H
,
.
Prevalence of c. 1559delT in ALPL, a common mutation resulting in the perinatal (lethal) form of hypophosphatasia in Japanese and effects of the mutation on heterozygous carriers
.
J Hum Genet
.
2011
;
56
(
2
):
166
8
.
13.
Greenberg
CR
,
Taylor
CL
,
Haworth
JC
,
Seargeant
LE
,
Philipps
S
,
Triggs-Raine
B
,
.
A homoallelic Gly317→ Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites
.
Genomics
.
1993
;
17
(
1
):
215
7
.
14.
Greenberg
CR
,
Evans
JA
,
McKendry-Smith
S
,
Redekopp
S
,
Haworth
JC
,
Mulivor
R
,
.
Infantile hypophosphatasia: localization within chromosome region 1p36.1–34 and prenatal diagnosis using linked DNA markers
.
Am J Hum Genet
.
1990
;
46
(
2
):
286
92
.
15.
Klauke
AL
,
Racz
I
,
Pradier
B
,
Markert
A
,
Zimmer
AM
,
Gertsch
J
.
The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain
.
Eur Neuropsychopharmacol
.
2014
;
24
(
4
):
608
20
.
16.
Costa
B
,
Colleoni
M
,
Conti
S
,
Parolaro
D
,
Franke
C
,
Trovato
AE
,
.
Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw
.
Naunyn Schmiedebergs Arch Pharmacol
.
2004
;
369
(
3
):
294
9
.
17.
Atalay
S
,
Jarocka-Karpowicz
I
,
Skrzydlewska
E
.
Antioxidative and anti-inflammatory properties of cannabidiol
.
Antioxidants
.
2019
;
9
(
1
):
21
.
18.
De Petrocellis
L
,
Ligresti
A
,
Moriello
AS
,
Allarà
M
,
Bisogno
T
,
Petrosino
S
,
.
Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes
.
Br J Pharmacol
.
2011
;
163
(
7
):
1479
94
.
19.
Pellati
F
,
Borgonetti
V
,
Brighenti
V
,
Biagi
M
,
Benvenuti
S
,
Corsi
L
.
Cannabis sativa L. and nonpsychoactive cannabinoids: their chemistry and role against oxidative stress, inflammation, and cancer
.
Biomed Res Int
.
2018
;
2018
:
1691428
.
20.
Sholler
DJ
,
Schoene
L
,
Spindle
TR
.
Therapeutic efficacy of cannabidiol (CBD): a review of the evidence from clinical trials and human laboratory studies
.
Curr Addict Rep
.
2020
;
7
(
3
):
405
12
.
21.
Oláh
A
,
Tóth
BI
,
Borbíró
I
,
Sugawara
K
,
Szöllõsi
AG
,
Czifra
G
,
.
Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes
.
J Clin Invest
.
2014
;
124
(
9
):
3713
24
.
22.
Girschick
HJ
,
Seyberth
HW
,
Huppertz
HI
.
Treatment of childhood hypophosphatasia with nonsteroidal antiinflammatory drugs
.
Bone
.
1999
;
25
(
5
):
603
7
.
23.
Rush
ET
.
Childhood hypophosphatasia: to treat or not to treat
.
Orphanet J Rare Dis
.
2018
;
13
(
1
):
116
5
.
24.
Mornet
E
,
Nunes
ME
.
Hypophosphatasia
.
Seattle (WA)
:
University of Washington
;
1993
.
25.
Takeda
S
,
Misawa
K
,
Yamamoto
I
,
Watanabe
K
.
Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis
.
Drug Metab Dispos
.
2008
;
36
(
9
):
1917
21
.
26.
Burstein
S
.
Cannabidiol (CBD) and its analogs: a review of their effects on inflammation
.
Bioorg Med Chem
.
2015
;
23
(
7
):
1377
85
.
27.
Kearney
PM
,
Baigent
C
,
Godwin
J
,
Halls
H
,
Emberson
JR
,
Patrono
C
.
Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials
.
BMJ
.
2006
;
332
(
7553
):
1302
8
.
28.
Trelle
S
,
Reichenbach
S
,
Wandel
S
,
Hildebrand
P
,
Tschannen
B
,
Villiger
PM
,
.
Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis
.
BMJ
.
2011
;
342
:
c7086
.
29.
Rostom
A
,
Dube
C
,
Wells
GA
,
Tugwell
P
,
Welch
V
,
Jolicoeur
E
,
.
Prevention of NSAID-induced gastroduodenal ulcers
.
Cochrane Database Syst Rev
.
2002
;(
104
):
CD002296
.
30.
Traversa
G
,
Walker
AM
,
Ippolito
FM
,
Caffari
B
,
Capurso
L
,
Dezi
A
,
.
Gastroduodenal toxicity of different nonsteroidal antiinflammatory drugs
.
Epidemiology
.
1995
;
6
(
1
):
49
54
.
31.
MacCallum
CA
,
Russo
EB
.
Practical considerations in medical cannabis administration and dosing
.
Eur J Intern Med
.
2018
;
49
:
12
9
.
32.
Legault
J
,
Pichette
A
.
Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel
.
J Pharm Pharmacol
.
2007
;
59
(
12
):
1643
7
.
33.
Bahi
A
,
Al Mansouri
S
,
Al Memari
E
,
Al Ameri
M
,
Nurulain
SM
,
Ojha
S
.
β-caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice
.
Physiol Behav
.
2014
;
135
:
119
24
.
34.
Al Mansouri
S
,
Ojha
S
,
Al Maamari
E
,
Al Ameri
M
,
Nurulain
SM
,
Bahi
A
.
The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice
.
Pharmacol Biochem Behav
.
2014
;
124
:
260
8
.
35.
Schmidt-Wolf
G
,
Cremer-Schaeffer
P
.
[Three years of cannabis as medicine-preliminary results of the survey accompanying the prescription of medical cannabis in Germany]
.
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz
.
2021
;
64
(
3
):
368
77
.
36.
Grotenhermen
F
.
Pharmacokinetics and pharmacodynamics of cannabinoids
.
Clin Pharmacokinet
.
2003
;
42
(
4
):
327
60
.
37.
National Health Service England
.
Barriers to accessing cannabis-based products for medicinal use on NHS prescription
.
England
:
NHS England and NHS Improvement
;
2019
. p.
7
.
38.
Ebbert
JO
,
Scharf
EL
,
Hurt
RT
.
Medical cannabis
.
Mayo Clinic Proc
.
2018
;
93
(
12
):
1842
47
.
39.
Arboleda
MF
,
Prosk
E
,
Cyr
C
,
Gamaoun
R
,
Vigano
A
.
Medical cannabis in supportive cancer care: lessons from Canada
.
Support Care Cancer
.
2020
;
28
(
7
):
2999
3001
.
40.
Pardo
B
.
Cannabis policy reforms in the Americas: a comparative analysis of Colorado, Washington, and Uruguay
.
Int J Drug Policy
.
2014
;
25
(
4
):
727
35
.
41.
Lucas
P
,
Reiman
A
,
Earleywine
M
,
McGowan
SK
,
Oleson
M
,
Coward
MP
,
.
Cannabis as a substitute for alcohol and other drugs: a dispensary-based survey of substitution effect in Canadian medical cannabis patients
.
Addict Res Theory
.
2013
;
21
(
5
):
435
42
.
42.
Flexon
JL
,
Stolzenberg
L
,
D’Alessio
SJ
.
The effect of cannabis laws on opioid use
.
Int J Drug Policy
.
2019
;
74
:
152
9
.
43.
Zylla
D
,
Steele
G
,
Eklund
J
,
Mettner
J
,
Arneson
T
.
Oncology clinicians and the minnesota medical cannabis program: a survey on medical cannabis practice patterns, barriers to enrollment, and educational needs
.
Cannabis Cannabinoid Res
.
2018
;
3
(
1
):
195
202
.
44.
Braun
IM
,
Wright
A
,
Peteet
J
,
Meyer
FL
,
Yuppa
DP
,
Bolcic-Jankovic
D
,
.
Medical oncologists’ beliefs, practices, and knowledge regarding marijuana used therapeutically: a nationally representative survey study
.
J Clin Oncol
.
2018
;
36
(
19
):
1957
62
.
45.
Karanges
EA
,
Suraev
A
,
Elias
N
,
Manocha
R
,
McGregor
IS
.
Knowledge and attitudes of Australian general practitioners towards medicinal cannabis: a cross-sectional survey
.
BMJ Open
.
2018
;
8
(
7
):
e022101
.
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